Abstract
Antigen-specific receptors on T lymphocytes are generated by the rearrangement of germline DNA to produce immunoglobulinhke receptor molecules. Unlike the immunoglobulin receptors on B cells, however, T cells do not secrete antigen-specific molecules but rather express them only on the cell surface. Furthermore, unlike immunoglobulins, which can recognize virtually any form of antigen, be it on the cell surface, soluble in the plasma, protein, or carbohydrate, the T-cell receptor (TCR) recognizes protein antigen that is processed into peptides and complexed together with class I or class 11 molecules on the cell surface. Thus, T cells must be capable of “reading” and interpreting class I/lI-peptide complexes, and be capable of determining if these complexes indicate that trouble is lurking within the cell. This remarkable ability of T cells to analyze the actual contents of cells defines their role as highly specialized detectives capable of routing our intracellular pathogens. Once cells harboring intracellular pathogens are discovered, T cells can differentiate specific cytotoxic activity and destroy infected cells.
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References
Hedrick, S. M., Nielsen, E. A., Kavaler, J., Cohen, D. I., and Davis, M. M. 1984. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature 308:153–158.
Chien, Y. H., and Davis, M. M. 1993. How alpha beta T-cell receptors’ see’ peptide/MHC complexes. Immunol. Today 14:597–602.
Davis, M. M., and Bjorkman, P. J. 1988. T-cell antigen receptor genes and T-cell recognition. Nature 334:395–402.
Hedrick, S. M., Cohen, D. I., Nielsen, E. A., and Davis, M. M. 1984. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature 308:149–153.
Yanagi, Y., Yoshikai, Y., Legget, K., Clark, S., Aleksander, I., and Mak, T. W. 1984. A human T cell-specific cDNA encodes a protein with partial homology to immunoglobulin chain. Nature 308:145–149.
Davis, M. M. 1990. T cell receptor gene diversity and selection. Annu. Rev. Biochem. 59:475–496.
Kronenberg, M., Sui, G., Hood, L. E., and Shastri, N. 1986. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annu. Rev. Immunol. 4:529–554.
Toyonaga, B., and Mak, T. W. 1987. Genes of the T-cell antigen receptor in normal and malignant T cells. Annu. Rev. Immunol. 5:585–620.
Patten, P., Yokota, T., Rothbard, J., Chien, Y., Arai, K., and Davis, M. M. 1984. Structure, expression and divergence of T-cell receptor beta-chain variable regions. Nature 312:40–46.
Chothia, C., Boswell, D. R., and Lesk, A. M. 1988. The outline structure of the T-cell αβ receptor. EMBO J. 7:3745–3755.
Hedrick, S. M., Engel, I., McElligott, D. L., Fink, P. J., Hsu, M. L., Hansburg, D., and Malis, L. A. 1988. Selection of amino acid sequences in the beta chain of the T cell antigen receptor. Science 239:1541–1544.
Ruberti, G., Paragas, V., Kim, D., and Fathman, C. G. 1993. Selection of amino acid sequence and J beta element usage in the beta chain of DBA/2V beta b-and DBA/2V beta a-derived myoglobin-specific T cell clones. J. Immunol. 151:6185–6194.
Currier, J. R., Deulofeut, H., Barron, K. S., Kehn, P. J., and Robinson, M. A. 1996. Mitogens, superantigens, and nominal antigens elicit distinctive patterns of TCRβ CDR3 diversity. Hum. Immunol. 48:39–51.
Moss, P. A. H., and Bell, J. I. 1996. Comparative sequence-analysis of the human T-cell receptor TCRα and TCRβ CDR3 regions. Hum. Immunol. 48:32–38.
Wither, J., Pawling, J., Phillips, L., Delovitch, T., and Hozumi, N. 1991. Amino acid residues in the T cell receptor CDR3 determine the antigenic reactivity patterns of insulin-reactive hybridomas. J. Immunol. 146:3513–3522.
Lai, M. Z., Jang, Y. J., Chen, L. K., and Gefter, M. L. 1990. Restricted V-(D)-J junctional regions in the T cell response to lambda-repressor. Identification of residues critical for antigen recognition. J. Immunol. 144:4851–4856.
Candeias, S., Waltzinger, C., Benoist, C., and Mathis, D. 1991. The V beta 17+ T cell repertoire: Skewed J beta usage after thymic selection; dissimilar CDR3s in CD4+ versus CD8+ cells. J. Exp. Med. 174:989–1000.
Yamada, M., Wasserman, R., Reichard, B. A., Shane, S., Caton, A. J., and Rovera, G. 1991. Preferential utilization of specific immunoglobulin heavy chain diversity and joining segments in adult human peripheral blood B lymphocytes. J. Exp. Med. 173:395–407.
Brenner, M. B., Strominger, J. L., and Krangel, M. S. 1988. The gamma delta T cell receptor. Adv. Immunol. 43:133–192.
Haas, W., Kaufman, S., and Martinez, A. C. The development and function of gamma/delta T cells. Immunol. Today 11:340–343.
Raulet, D. H. 1989. The structure, function and molecular genetics of the gamma/delta T cell receptor. Annu. Rev. Immunol. 7:175–207.
Rocha, B., and von Boehmer, H. 1991. Peripheral selection of the T cell repertoire. Science 251:1225–1228.
Kirberg, J., Swat, W., Rocha, B., Kisielow, P., and von Boehmer, H. 1993. Induction of tolerance in immature and mature T cells. Transplant Proc. 25:279–280.
Rocha, B., Grandien, A., and Freitas, A. A. 1995. Anergy and exhaustion are independent mechanisms of peripheral T cell tolerance. J. Exp. Med. 181:993–1003.
Schwartz, R. H. 1989. Acquisition of immunologic self-tolerance. Cell 57:1073–1081.
Webb, S., Morris, C., and Sprent, J. 1990. Extrathymic tolerance of mature T cells: Clonal elimination as a consequence of immunity. Cell 63:1249–1256.
Sprent, J., and Webb, S. R. 1995. Intrathymic and extrathymic clonal deletion of T-cells. Curr. Opin. Immunol. 7:196–205.
Wegener, A. M., Letourneur, F., Hoeveler, A., Brocker, T., Luton, F., and Malissen, B. 1992. The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules. Cell 68:83–95.
Ohashi, P. S., Mak, T. W., van den Elsen, P., Yanagi, Y., Yoshikai, Y., Calman, A. F., Terhorst, C., Stobo, J. D., and Weiss, A. 1985. Reconstitution of an active surface T3/T-cell antigen receptor by DNA transfer. Nature 316:606–609.
Saito, T., Weiss, A., Miller, J., Norcross, M. A., and Germain, R. N. 1987. Specific antigen-la activation of transfected human T cells expressing murine Ti alpha beta-human T3 receptor complexes. Nature 325:125–130.
Mariuzza, R. A., and Winter, G. 1989. Secretion of a homodimeric V alpha C kappa T-cell receptor-immunoglobulin chimeric protein. J. Biol. Chem. 264:7310–7316.
Gregoire, C., Rebaie, N., Schweisguth, F., Necker, A., Mazza, G., Auphan, N., Millward, A., Schmitt Verhulst, A. M., and Malissen, B. 1991. Engineered secreted T-cell receptor alpha beta heterodimers. Proc. Natl. Acad. Sci. USA 88:8077–8081.
Engel, I., Ottenhoff, T. H., and Klausner, R. D. 1992. High-efficiency expression and solubilization of functional T cell antigen receptor heterodimers. Science 256:1318–1321.
Bentley, G. A., Boulot, G., Karjalainen, K., and Mariuzza, R. A. 1995. Crystal struclure of the beta chain of a T cell antigen receptor. Science 267:1984–1987.
Malchiodi, E. L., Eisenstein, E., Fields, B. A., Ohlendorf, D. H., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. A. 1995. Superantigen binding to a T cell receptor beta chain of known three-dimensional structure. J. Exp. Med. 182:1833–1845.
Fields, B. A., and Mariuzza, R. A. 1996. Structure and function of the T-cell receptor—Insights from x-ray crystallography. Immunol. Today 17:330–336.
Harpaz, Y., and Chothia, C. 1994. Many of the immunoglobulin superfamily domains in cell adhesion molecules and surface receptors belong to a new structural set which is close to that containing variable domains. J. Mol. Biol. 238:528–539.
Bork, P., Holm, L., and Sander, C. 1994. The immunoglobulin fold. Structural classification, sequence patterns and common core. J. Mol. Biol. 242:309–320.
Saito, H., Kranz, D. M., Takagaki, Y., Hayday, A., Eisen, H., and Tonegawa, S. 1984. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature 312:36–41.
Chien, Y. H., Iwashima, M., Kaplan, K. B., Elliott, J. F., and Davis, M. M. 1987. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. Nature 327:677–682.
Korman, A. J., Maruyama, J., and Raulet, D. H. 1989. Rearrangement by inversion of the T-cell receptor delta variable region gene located 3’ of the delta constant region gene. Proc. Natl. Acad. Sci. USA 86:267–271.
Brenner, M. B., McLean, J., Dialynas, D. P., Strominger, J. L., Smith, J. A., Owen, F. L., Seidman, J. G., Ip, S., Rosen, F., and Krangel, M. S. 1986. Identification of a putative second T cell receptor. Nature 322:145–149.
Arden, B., Clark, S. P., Kabelitz, D., and Mak, T. W. 1995. Human T-cell receptor variable gene segment families. Immunogenetics 42:455–500.
Koop, B. F., Rowen, L., Wang, K., Kuo, C. L., Seto, D., Lenstra, J. A., Howard, S., Shan, W., Deshpande, P., and Hood, L. 1994. The human T-cell receptor TCRAC/TCRDC (cAlpha/cDelta) region: organization, sequence, and evolution of 97.6 kb of DNA. Genomics 19:478–493.
Rowen, L., Koop, B. F., and Hood, L. 1996. The complete 685-kilobase DNA sequence of the human β T cell receptor locus. Science 272:1755–1762.
Arden, B., Clark, S. P., Kabelitz, D., and Mak, T. W. 1995. Mouse T-cell receptor variable gene segment families. Immunogenetics 42:501–530.
Yoshikai, Y., Anatoniou, D., Clark, S. P., Yanagi, Y., Sangster, R., Van den Elsen, P., Terhorst, C., and Mak, T. W. 1984. Sequence and expression of transcripts of the human T-cell receptor beta-chain genes. Nature 312:521–524.
Uematsu, Y., Ryser, S., Dembic, Z., Borgulya, P., Krimpenfort, P., Berns, A., von Boehmer, H., and Steinmetz, M. 1988. In transgenic mice the introduced functional T cell receptor beta gene prevents expression of endogenous beta genes. Cell 52:831–841.
Krimpenfort, P., Ossendorp, F., Borst, J., Melief, C., and Berns, A. 1989. T cell depletion in transgenic mice carrying a mutant gene for TCR-beta. Nature 341:742–746.
Borgulya, P., Kishi, H., Uematsu, Y., and von Boehmer, H. 1992. Exclusion and inclusion of alpha and beta T cell receptor alleles. Cell 69:529–537.
LeFranc, M. P., and Rabbitts, T. H. 1989. The human T cell receptor gamma (TCRG) genes. Biochem. Trends Sci. 14:214–218.
Haas, W., Pereira, P., and Tonegawa, S. 1993. Gamma/delta cells. Annu. Rev. Immunol. 11:637–685.
Hayday, A. C., Saito, H., Gillies, S. D., Kranz, D. M., Tanigawa, G., Eisen, H. N., and Tonegawa, S. 1985. Structure, organization, and somatic rearrangement of T cell gamma genes. Cell 40:259–269.
Garman, R. D., Doherty, P. J., and Raulet, D. H. 1986. Diversity, rearrangement, and expression of murine T cell gamma genes. Cell 45:733–742.
Iwamoto, A., Rupp, F., Ohashi, P. S., Walker, C. L., Pircher, H., Joho, R., Hengartner, H., and Mak, T. W. 1986. T cell-specific gamma genes in C57BL/10 mice. Sequence and expression of new constant and variable region genes. J. Exp. Med. 163:1203–1212.
Kuziel, W. A., Takashima, A., Bonyhadi, M., Bergstresser, P. R., Allison, J. P., Tigelaar, R. E., and Tucker, P. W. 1987. Regulation of T-cell receptor gamma-chain RNA expression in murine Thyl+ dendritic epidermal cells. Nature 328:262–266.
Lieber, M. R. 1992. The mechanism of V(D)J recombination: A balance of diversity, specificity, and stability. Cell 70:873–876.
Roth, D. B., and Wilson, J. H. 1986. Nonhomologous recombination in mammalian cells: Role for short sequence homologies in the joining reaction. Mol. Cell. Biol. 6:4295–4304.
Raulet, D. H., Spencer, D. M., Hsiang, Y. H., Goldman, J. P., Bix, M., Liao, N. S., Zijlstra, M., Jaenisch, R., and Correa, I. 1991. Control of gamma delta T-cell development. Immunol. Rev. 120:185–204.
Zhang, Y., Cado, D., Asarnow, D. M., Komori, T., Alt, F. W., Raulet, D. H., and Allison, J. P. 1995. The role of short homology repeats and TdT in generation of the invariant gamma-delta antigen receptor repertoire in the fetal thymus. Immunity 3:439–447.
Allison, J. P., and Havran, W. L. 1991. The immunobiology of T cells with invariant gamma delta antigen receptors. Annu. Rev. Immunol. 9:679–705.
Sim, G. K., and Augustin, A. 1990. Dominantly inherited expression of BID, an invariant undiversified T cell receptor delta chain. Cell 61:397–405.
Kaufmann, S. H. E. 1996. Gamma/delta and other unconventional T-lymphocytes—What do they see and what do they do. Proc. Natl. Acad. Sci. USA 93:2272–2279.
Rock, E. P., Sibbald, P. R., Davis, M. M., and Chien, Y. H. 1994. CDR3 length in antigen-specific immune receptors. J. Exp. Med. 179:323–328.
Schild, H., Mavaddat, N., Litzenberger, C., Ehrich, E. W., Davis, M. M., Bluestone, J. A., Matis, L., Draper, R. K., and Chien, Y. H. 1994. The nature of major histocompatibility complex recognition by gamma delta T cells. Cell 76:29–37.
Bonyhadi, M., Weiss, A., Tucker, P. W., Tigelaar, R. E., and Allison, J. P. 1987. Delta is the Cx-gene product in the gamma/delta antigen receptor of dendritic epidermal cells. Nature 330:574–576.
Asarnow, D. M., Goodman, T., Lefrancois, L., and Allison, J. P. 1989. Distinct antigen receptor repertoires of two classes of murine epithelial associated T-cells. Nature 341:60–62.
Kyes, S., Carew, E., Carding, S. R., Janeway, C. A., Jr., and Hayday, A. 1989. Diversity in T-cell receptor gamma gene usage in intestinal epithelium. Proc. Natl. Acad. Sci. USA 86:5527–5531.
Itohara, S., Farr, A. G., Lafaille, J. J., Bonneville, M., Takagaki, Y., Haas, W., and Tonegawa, S. 1990. Homing of a gamma delta thymocyte subset with homogeneous T-cell receptors to mucosal epithelia. Nature 343:754–757.
Sim, G. K. 1995. Intraepithelial lymphocytes and the immune system. Adv. Immunol. 58:297–343.
Havran, W. L., and Boismenu, R. 1994. Activation and function of gamma delta T cells. Curr. Opin. Immunol. 6:442–446.
Stingl, G., Gunter, K. C., Tschachler, E., Yamada, H., Lechler, R. I., Yokoyama, W. M., Steiner, G., Germain, R. N., and Shevach, E. M. 1987. Thy-1+ dendritic epidermal cells belong to the T-cell lineage. Proc. Natl. Acad. Sci. USA 84:2430–2434.
Ferrick, D. A., Ohashi, P. S., Wallace, V., Schilham, M., and Mak, T. W. 1989. Thymic ontogeny and selection of alpha beta and gamma delta T cells. Immunol. Today 10:403–407.
Kronenberg, M. 1994. Antigens recognized by gamma delta T cells. Curr. Opin. Immunol. 6:64–71.
Kozbor, D., Trinchieri, G., Monos, D. S., Isobe, M., Russo, G., Haney, J. A., Zmijewski, C., and Croce, C. M. 1989. Human TCR-gamma+/delta+, CD8+ T lymphocytes recognize tetanus toxoid in an MHC-restricted fashion. J. Exp. Med. 169:1847–1851.
Holoshitz, J., Koning, F., Coligan, J. E., De Bruyn, J., and Strober, S. 1989. Isolation of CD4-CD8-mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature 339:226–229.
Matis, L. A., Fry, A. M., Cron, R. Q., Cotterman, M. M., Dick, R. F., and Bluestone, J. A. 1989. Structure and specificity of a class II MHC alloreactive gamma delta T cell receptor heterodimer. Science 245:746–749.
Guo, Y., Ziegler, H. K., Safley, S. A., Niesel, D. W., Vaidya, S., and Klimpel, G. R. 1995. Human T-cell recognition of Listeria monocytogenes: Recognition of listeriolysin O by TcR alpha beta+ and TcR gamma delta+ T cells. Infect. Immun. 63:2288–2294.
Vidovic, D., Roglic, M., McKune, K., Guerder, S., MacKay, C., and Dembic, Z. 1989. Qa-1 restricted recognition of foreign antigen by a gamma delta T-cell hybridoma. Nature 340:646–650.
Imani, F., and Soloski, M. J. 1991. Heat shock proteins can regulate expression of the Tla region-encoded class lb molecule Qa-1. Proc. Natl. Acad. Sci. USA 88:10475–10479.
Soloski, M. J., DeCloux, A., Aldrich, C. J., and Forman, J. 1995. Structural and functional characteristics of the class Ib molecule, Qa-1. Immunol. Rev. 147:67–89.
Davis, M. M., and Chien, Y. 1995. Issues concerning the nature of antigen recognition by alpha beta and gamma delta T-cell receptors. Immunol. Today 16:316–318.
Sciammas, R., Johnson, R. M., Sperling, A. I., Brady, W., Linsley, P. S., Spear, P. G., Fitch, F. W., and Bluestone, J. A. 1994. Unique antigen recognition by a herpesvirus-specific TCR-gamma delta cell. J. Immunol. 152:5392–5397.
Pfeffer, K., Schoel, B., Gulle, H., Kaufmann, S. H., and Wagner, H. 1990. Primary responses of human T cells to mycobacteria: A frequent set of gamma/delta T cells are stimulated by protease-resistant ligands. Eur. J. Immunol. 20:1175–1179.
Morita, C. T., Beckman, E. M., Bukowski, J. F., Tanaka, Y., Band, H., Bloom, B. R., Golan, D. E., and Brenner, M. B. 1995. Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells. Immunity 3:495–507.
Tsukaguchi, K., Balaji, K. N., and Boom, W. H. 1995. CD4+ alpha beta T cell and gamma delta T cell responses to Mycobacterium tuberculosis. Similarities and differences in Ag recognition, cytotoxic effector function, and cytokine production. J. Immunol. 154:1780–1796.
Follows, G. A., Munk, M. E., Gatrill, A. J., Conradt, P., and Kaufmann, S. H. 1992. Gamma interferon and interleukin 2, but not interleukin 4, are detectable in gamma/delta T-cell cultures after activation with bacteria. Infect. Immun. 60:1229–1231.
Skeen, M. J., and Ziegler, H. K. 1995. Activation of gamma delta T cells for production of IFN-gamma is mediated by bacteria via macrophage-derived cytokines IL-1 and IL-12. J. Immunol. 154:5832–5841.
Ferrick, D. A., Schrenzel, M. D., Mulvania, T., Hsieh, B., Ferlin, W. G., and Lepper, W. 1995. Differential production of interferon-gamma and interleukin-4 in response to TH1-stimulating and TH2-stimulating pathogens by gamma-delta T-cells in-vivo. Nature 373:255–257.
Kawamoto, Y., Sasaki, K., Kato, Y., Kojima, K., Tsuji, T., and Miyama, A. 1996. Rapid killing of murine lymph node T blasts by intestinal intraepithelial lymphocytes in vitro. Eur. J. Immunol. 26:653–658.
Nakajima, H., Tomiyama, H., and Takiguchi, M. 1995. Inhibition of gamma delta T cell recognition by receptors for MHC class I molecules. J. Immunol. 155:4139–4142.
Munk, M. E., Gatrill, A. J., and Kaufmann, S. H. 1990. Target cell lysis and IL-2 secretion by gamma/delta T lymphocytes after activation with bacteria. J. Immunol. 145:2434–2439.
Subauste, C. S., Chung, J. Y., Do, D., Koniaris, A. H., Hunter, C. A., Montoya, J. G., Porcelli, S., and Remington, J. S. 1995. Preferential activation and expansion of human peripheral blood gamma delta T cells in response to Toxoplasma gondii in vitro and their cytokine production and cytotoxic activity against T. gondii-infected cells. J. Clin. Invest. 96:610–619.
Penninger, J. M., Wen, T., Timms, E., Potter, J., Wallace, V. A., Matsuyama, T., Ferrick, D., Sydora, B., Kronenberg, M., and Mak, T. W. 1995. Spontaneous resistance to acute T-cell leukemias in TCRV-gamma-1.1J-gamma-4C-gamma-4 transgenic mice. Nature 375:241–244.
Mombaerts, P., Arnoldi, J., Russ, F., Tonegawa, S., and Kaufmann, S. H. 1993. Different roles of alpha beta and gamma delta T cells in immunity against an intracellular bacterial pathogen. Nature 365:53–56.
Kabelitz, D., Bender, A., Schondelmaier, S., Schoel, B., and Kaufmann, S. H. 1990. A large fraction of human peripheral blood gamma/delta + T cells is activated by Mycobacterium tuberculosis but not by its 65-kD heat shock protein. J. Exp. Med. 171:667–679.
Lima, E. C. S., and Minoprio, P. 1996. Chagas disease is attenuated in mice lacking gamma-delta T-cells. Infect. Immun. 64:215–221.
Raine, C. S., Wu, E., Ivanyi, J., Katz, D., and Brosnan, C. F. 1996. Multiple sclerosis—A protective or a pathogenic role for heat-shock protein 60 in the central nervous system. Lab. Invest. 75:109–123.
Martins, E. B. G., Graham, A. K., Chapman, R. W., and Fleming, K. A. 1996. Elevation of gamma-delta T-lymphocytes in peripheral blood and livers of patients with primary sclerosing cholangitis and other autoimmune liver diseases. Hepatology 23:988–993.
Stinissen, P., Vandevyver, C., Medaer, R., Vandegaer, L., Nies, J., Tuyls, L., Hafler, D. A., Raus, J., and Zhang, J. W. 1995. Increased frequency of gamma-delta T-cells in cerebrospinal fluid and peripheral blood of patients with multiple sclerosis reactivity, cytotoxicity, and T-cell receptor v gene rearrangements. J. Immunol. 154:4883–4894.
Ohga, S., Yoshikai, Y., Takeda, Y., Hiromatsu, K., and Nomoto, K. 1990. Sequential appearance of gamma/delta-and alpha/beta-bearing T cells in the peritoneal cavity during an i.p. infection with Listeria monocytogenes. Eur. J. Immunol. 20:533–538.
Fujimoto, S., and Yamagishi, H. 1987. Isolation of an excision product of T-cell receptor alpha-chain gene rearrangements. Nature 327:242–243.
Okazaki, K., and Sakano, H. 1988. Thymocyte circular DNA excised from T cell receptor alpha-delta gene complex. EMBO J. 7:1669–1674.
Malissen, M., McCoy, C., Blanc, D., Trucy, J., Devaux, C., Schmitt-Verhulst, A. M., Pitch, F., Hood, L., and Malissen, B. 1986. Direct evidence for chromosomal inversion during T cell receptor beta-gene rearrangements. Nature 319:28–33.
Tonegawa, S. 1983. Somatic generation of antibody diversity. Nature 302:575–581.
Raulet, D. H., Garman, R. D., Saito, H., and Tonegawa, S. 1985. Developmental regulation of T-cell receptor gene expression. Nature 314:103–107.
Haas, W., and Tonegawa, S. 1992. Development and selection of gamma delta T cells. Curr. Opin. Immunol. 4:147–155.
Philpott, K. L., Viney, J. L., Kay, G., Rastan, S., Gardiner, E. M., Chae, S., Hayday, A. C., and Owen, M. J. 1992. Lymphoid development in mice congenitally lacking T cell receptor alpha beta-expressing cells. Science 256:1448–1452.
Winoto, A., and Baltimore, D. 1989. Separate lineages of T cells expressing the alpha beta and gamma delta receptors. Nature 338:430–432.
Snodgrass, H. R., Dembic, Z., Steinmetz, M., and von Boehmer, H. 1985. Expression of T-cell antigen receptor genes during fetal development in the thymus. Nature 315:232–233.
Chien, Y. H., Iwashima, M., Wettstein, D. A., Kaplan, K. B., Elliott, J. F., Born, W., and Davis, M. M. 1987. T-cell receptor delta gene rearrangements in early thymocytes. Nature 330:722–727.
Krangel, M. S., Yssel, H., Brocklehurst, C., and Spits, H. 1990. A distinct wave of human T cell receptor gamma/delta lymphocytes in the early fetal thymus: Evidence for controlled gene rearrangement and cytokine production. J. Exp. Med. 172:847–859.
Pearse, M., Wu, L., Egerton, M., Wilson, A., Shortman, K., and Scollay, R. 1989. A murine early thymocyte developmental sequence is marked by transient expression of the interleukin 2 receptor. Proc. Natl. Acad. Sci. USA 86:1614–1618.
Held, W., Mueller, C., and MacDonald, H. R. 1990. Expression of T cell receptor genes in the thymus: Localization of transcripts in situ and comparison of mature and immature subsets. Eur. J. Immunol. 20:2133–2136.
Petrie, H. T., Scollay, R., and Shortman, K. 1992. Commitment to the T cell receptor-alpha beta or-gamma delta lineages can occur just prior to the onset of CD4 and CD8 expression among immature thymocytes. Eur. J. Immunol. 22:2185–2188.
Ferrier, P., Krippl, B., Blackwell, T. K., Furley, A. J., Suh, H., Winoto, A., Cook, W. D., Hood, L., Costantini, F., and Alt, F. W. 1990. Separate elements control DJ and VDJ rearrangement in a transgenic recombination substrate. EMBO J. 9:117–125.
Lauzurica, P., and Krangel, M. S. 1994. Temporal and lineage-specific control of T cell receptor alpha/delta gene rearrangement by T cell receptor alpha and delta enhancers. J. Exp. Med. 179:1913–1921.
Capone, M., Watrin, F., Fernex, C., Horvat, B., Krippl, B., Wu, L., Scollay, R., and Ferrier, P. 1993. TCR beta and TCR alpha gene enhancers confer tissue-and stage-specificity on V(D)J recombination events. EMBO J. 12:4335–4346.
Bories, J. C., Demengeot, J., Davidson, L., and Alt, F. W. 1996. Gene-targeted deletion and replacement mutations of the T-cell receptor beta-chain enhancer—The role of enhancer elements in controlling V(D)J recombination accessibility. Proc. Natl. Acad. Sci. USA 93:7871–7876.
Sleckman, B. P., Gorman, J. R., and Alt, F. W. 1996. Accessibility control of antigen-receptor variable-region gene assembly—Role of cis-acting elements. Annu. Rev. Immunol. 14:459–481.
Okada, A., Mendelsohn, M., and Alt, F. 1994. Differential activation of transcription versus recombination of transgenic T cell receptor beta variable region gene segments in B and T lineage cells. J. Exp. Med. 180:261–272.
Ishida, I., Verbeek, S., Bonneville, M., Itohara, S., Berns, A., and Tonegawa, S. 1990. T-cell receptor gamma delta and gamma transgenic mice suggest a role of a gamma gene silencer in the generation of alpha beta T cells. Proc. Natl. Acad. Sci. USA 87:3067–3071.
Ho, I. C., Yang, L. H., Morie, G., and Leiden, J. M. 1989. A T-cell-specific transcriptional enhancer element 3’ of C alpha in the human T-cell receptor alpha locus. Proc. Natl. Acad. Sci. USA 86:6714–6718.
Winoto, A., and Baltimore, D. 1989. Alpha beta lineage-specific expression of the alpha T cell receptor gene by nearby silencers. Cell 59:649–655.
Takeda, J., Cheng, A., Mauxion, F., Nelson, C. A., Newberry, R. D., Sha, W. C., Sen, R., and Loh, D. 1990. Functional analysis of the murine T cell receptor beta enhancer and characteristic of its DNA-binding proteins. Mol. Cell. Biol. 10:5027–5035.
Marine, J., and Winoto, A. 1991. The human enhancer-binding protein Gata3 binds to several T-cell receptor regulatory elements. Proc. Natl. Acad. Sci. USA 88:7284–7288.
Hernandez-Munain, C., and Krangel, M. S. 1994. Regulation of the T-cell receptor delta enhancer by functional cooperation between c-Myb and core-binding factors. Mol. Cell. Biol. 14:473–483.
Hernandez-Munain, C., and Krangel, M. S. 1995. c-Myb and core-binding factor/PEBP2 display functional synergy but bind independently to adjacent sites in the T-cell receptor δ enhancer. Mol. Cell. Biol. 15:3090–3099.
Redondo, J. M., Hata, S., Brocklehurst, C., and Krangel, M. S. 1990. A T cell-specific transcriptional enhancer within the human T cell receptor delta locus. Science 247:1225–1229.
Hernandez-Munain, C., Lauzurica, P., and Krangel, M. S. 1996. Regulation of T-cell receptor delta-gene rearrangement by c-myb. J. Exp. Med. 183:289–293.
Lauzurica, P., and Krangel, M. S. 1994. Enhancer-dependent and-independent steps in the rearrangement of a human T cell receptor delta transgene. J. Exp. Med. 179:43–55.
Goldman, J. P., Spencer, D. M., and Raulet, D. H. 1993. Ordered rearrangement of variable region genes of the T cell receptor gamma locus correlates with transcription of the unrearranged genes. J. Exp. Med. 177:729–739.
Schatz, D. G., Oettinger, M. A., and Baltimore, D. 1989. The V(D)J recombination activating gene, RAG-1. Cell 59:1035–1048.
Oettinger, M. A., Schatz, D. G., Gorka, C., and Baltimore, D. 1990. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 248:1517–1523.
Lin, W. C., and Desiderio, S. 1993. Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation. Science 260:953–959.
Sadofsky, M. J., Hesse, J. E., McBlane, J. F., and Gellert, M. 1993. Expression and V(D)J recombination activity of mutated RAG-1 proteins. Nucleic Acids Res. 21:5644–5650.
Mombaerts, P., Iacomini, J., Johnson, R. S., Herrup, K., Tonegawa, S., and Papaioannou, V. E. 1992. RAG-1 deficient mice have no mature B and T lymphocytes. Cell 68:869–877.
Shinkai, Y., Rathbun, G., Lam, K. P., Oltz, E. M., Stewart, V., Mendelsohn, M., Charron, J., Datta, M., Young, F., Stall, A. M., and Alt, F. 1992. RAG-2 deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68:855–867.
Wilson, A., Held, W., and MacDonald, H. R. 1994. Two waves of recombinase gene expression in developing thymocytes. J. Exp. Med. 179:1355–1360.
Brandle, D., Muller, C., Rulicke, T., Hengartner, H., and Pircher, H. 1992. Engagement of the T-cell receptor during positive selection in the thymus down-regulates RAG-1 expression. Proc. Natl. Acad. Sci. USA 89:9529–9533.
Sadofsky, M. J., Hesse, J. E., Vangent, D. C., and Gellert, M. 1995. RAG-1 mutations that affect the target specificity of V(D)J recombination—A possible direct role of RAG-1 in site recognition. Genes Dev. 9:2193–2199.
Komori, T., Okada, A., Stewart, V., and Alt, F. W. 1993. Lack of N regions in antigen receptor variable region genes of TdT-deficient lymphocytes. Science 261:1171–1175.
Gilfillan, S., Dierich, A., LeMeur, M., Benoist, C., and Mathis, D. 1993. Mice lacking TdT: Mature animals with an immature lymphocyte repertoire. Science 261:1175–1178.
Gilfillan, S., Waltzinger, C., Benoist, C., and Mathis, D. 1994. More efficient positive selection of thymocytes in mice lacking terminal deoxynucleotidyl transferase. Int. Immunol. 6:1681–1686.
Gilfillan, S., Bachmann, M., Trembleau, S., Adorini, L., Kalinke, U., Zinkernagel, R., Benoist, C., and Mathis, D. 1995. Efficient immune-responses in mice lacking N-region diversity. Eur. J. Immunol. 25:3115–3122.
Rathmell, W. K., and Chu, G. 1994. A DNA end-binding factor involved in double-strand break repair and V(D)J recombination. Mol. Cell. Biol. 14:4741–4748.
Smider, V., Rathmell, W. K., Lieber, M. R., and Chu, G. 1994. Restoration of X-ray resistance and V(D)J recombination in mutant cells by Ku cDNA. Science 266:288–291.
Weaver, D. T. 1995. What to do at an end: DNA double-strand-break repair. Trends Genet. 11:388–392.
Ieggo, P. A., Taccioli, G. E., and Jackson, S. P. 1995. Menage-a-trois—Double-strand break repair, V(D)J recombination of DNA-PK. Bioessays 17:949–957.
Finnie, N. J., Gottlieb, T. M., Blunt, T., Jeggo, P. A., and Jackson, S. P. 1995. DNA-dependent protein-kinase activity is absent in xrs-6 cells—Implications for site-specific recombination and DNA double-strand break repair. Proc. Natl. Acad. Sci. USA 92:320–324.
Taccioli, G. E., Gottlieb, T. M., Blunt, T., Priestley, A., Demengeot, J., Mizuta, R., Lehmann, A. R., Alt, F. W., Jackson, S. P., and Jeggo, P. A. 1994. Ku80: Product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science 265:1442–1445.
Getts, R. C., and Stamato, T. D. 1994. Absence of a Ku-like DNA end binding activity in the xrs double-strand DNA repair-deficient mutant. J. Biol. Chem. 269:15981–15984.
Boubnov, N. V., and Weaver, D. T. 1995. SCID cells are deficient in Ku and replication protein A phosphorylation by the DNA-dependent protein kinase. Mol. Cell. Biol. 15:5700–5706.
Kirchgessner, C. U., Patil, C. K., Evans, J. W., Cuomo, C. A., Fried, L. M., Carter, T., Oettinger, M. A., and Brown, J. M. 1995. DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267:1178–1183.
Blunt, T., Finnie, N. J., Taccioli, G. E., Smith, G. C., Demengeot, J., Gottlieb, T. M., Mizuta, R., Varghese, A. J., Alt, F. W., Jeggo, P. A., and Jackson, S. P. 1995. Defective DNA-dependent protein-kinase activity is linked to V(D)J recombination and DNA-repair defects associated with the murine scid mutation. Cell 80:813–823.
Lees Miller, S. P., Godbout, R., Chan, D. W., Weinfeld, M., Day, R. S., 3rd, Barron, G. M., and Allalunis Turner, J. 1995. Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line. Science 267:1183–1185.
Nussenzweig, A., Chen, C. H., Soares, V. D., Sanchez, M., Sokol, K., Nussenzweig, M. C., and Li, G. C. 1996. Requirement for ku80 in growth and immunoglobulin V(D)J recombination. Nature 382:551–555.
Clevers, H., Alarcon, B., Wileman, T., and Terhorst, C. 1988. The T cell receptor/CD3 complex: A dynamic protein ensemble. Annu. Rev. Immunol. 6:629–662.
Koning, F., Maloy, W. L., and Coligan, J. E. 1990. The implications of subunit interactions for the structure of the T cell receptor-CD3 complex. Eur. J. Immunol. 20:299–305.
Blumberg, R. S., Ley, S., Sancho, J., Lonberg, N., Lacy, E., McDermott, F., Schad, V., Greenstein, J. L., and Terhorst, C. 1990. Structure of the T-cell antigen receptor: Evidence for two CD3 epsilon subunits in the T-cell receptor-CD3 complex. Proc. Natl. Acad. Sci. USA 87:7220–7224.
de la Hera, A., Muller, U., Olsson, C., Isaaz, S., and Tunnacliffe, A. 1991. Structure of the T cell antigen receptor (TCR): Two CD3 epsilon subunits in a functional TCR/CD3 complex. J. Exp. Med. 173:7–17.
Kappes, D. J., and Tonegawa, S. 1991. Surface expression of alternative forms of the TCR/CD3 complex. Proc. Natl. Acad. Sci. USA 88:10619–10623.
Weissman, A. M., Baniyash, M., Hou, D., Samelson, L. E., Burgess, W. H., and Klausner, R. D. 1988. Molecular cloning of the zeta chain of the T cell antigen receptor. Science 239:1018–1021.
Baniyash, M., Garcia-Morales, P., Bonifacino, J. S., Samelson, L. E., and Klausner, R. D. 1988. Disulfide linkage of the zeta and eta chains of the T cell receptors. J. Biol. Chem. 263:9874–9878.
Orloff, D. G., Frank, S. J., Robey, F. A., Weissman, A. M., and Klausner, R. D. 1989. Biochemical characterization of the eta chain of the T-cell receptor—A unique subunit related to zeta. J. Biol. Chem. 264:14812–14817.
Jin, Y. J., Clayton, L. K., Howard, F. D., Koyasu, S., Sieh, M., Steinbrich, R., Tarr, G. E., and Reinherz, E. L. 1990. Molecular cloning of the CD3 eta subunit identifies a CD3 zeta-related product in thymus-derived cells. Proc. Natl. Acad. Sci. USA 87:3319–3323.
Blank, U., Ra, C., Miller, L., White, K., Metzger, H., and Kinet, J. P. 1989. Complete structure and expression in transfected cells of high affinity IgE receptor. Nature 337:187–189.
Koyasu, S., D’Adamio, L., Arulanandam, A. R., Abraham, S., Clayton, L. K., and Reinherz, E. L. 1992. T cell receptor complexes containing Fc epsilon R1 gamma homodimers in lieu of CD3 zeta and CD3 eta components: A novel isoform expressed on large granular lymphocytes. J. Exp. Med. 175:203–209.
Ohno, H., Ono, S., Hirayama, N., Shimada, S., and Saito, T. 1994. Preferential usage of the Fc receptor gamma chain in the T cell antigen receptor complex by gamma/delta T cells localized in epithelia. J. Exp. Med. 179:365–377.
Bauer, A., McConkey, D. J., Howard, F. D., Clayton, L. K., Novick, D., Koyasu, S., and Reinherz, E. L. 1991. Differential signal transduction via T-cell receptor CD3 zeta2, CD3zeta-eta, and CD3 eta2 isoforms. Proc. Natl. Acad. Sci. USA 88:3842–3851.
Orloff, D. G., Ra, C. S., Frank, S. J., Klausner, R. D., and Kinet, J. P. 1990. Family of disulphide-linked dimers containing the zeta and eta chains of the T-cell receptor and the gamma chain of Fc receptors. Nature 347:189–191.
Ra, C., Jouvin, M. H., Blank, U., and Kinet, J. P. 1989. A macrophage Fc gamma receptor and the mast cell receptor for IgE share an identical subunit. Nature 341:752–754.
Ravetch, J. V., and Kinet, J. P. 1991. Fc receptors. Annu. Rev. Immunol. 9:457–492.
Hupp, K., Siwarski, D., Mock, B. A., and Kinet, J. P. 1989. Gene mapping of the three subunits of the high affinity FcR for IgE to mouse chromosomes 1 and 19. J. Immunol. 143:3787–3791.
Manolios, N., Kemp, O., and Li, Z. G. 1994. The T cell antigen receptor alpha and bela chains interact via distinct regions with CD3 chains. Eur. J. Immunol. 24:84–92.
Exley, M., Wileman, T., Mueller, B., and Terhorst, C. 1995. Evidence for multivalent structure of T-cell antigen receptor complex. Mol. Immunol. 32:829–839.
Williams, A. F., and Barclay, A. N. 1988. The immunoglobulin superfamily—Domains for cell surface recognition. Annu. Rev. Immunol. 6:381–405.
Weiss, A., and Littman, D. R. 1994. Signal transduction by lymphocyte antigen receptors. Cell 76:263–274.
Reth, M. 1989. Antigen receptor tail clue. Nature 338:383–384.
Chan, A. C., Irving, B. A., Fraser, J. D., and Weiss, A. 1991. The zeta chain is associated with a tyrosine kinase, and upon T cell antigen receptor stimulation associated with ZAP-70, and 70 kDa tyrosine phosphoprotein. Proc. Natl. Acad. Sci. USA 88:9166–9170.
Vivier, E., da Silva, A. J., Ackerly, M., Levine, H., Rudd, C. E., and Anderson, P. 1993. Association of a 70-kDa tyrosine phosphoprotein with the CD16: zeta: gamma complex expressed in human natural killer cells. Eur. J. Immunol. 23:1872–1876.
Straus, D. B., and Weiss, A. 1993. The CD3 chains of the T cell antigen receptor associate with the ZAP-70 tyrosine kinase and are tyrosine phosphorylated after receptor stimulation. J. Exp. Med. 178:1523–1530.
Buferne, M., Luton, F., Letourneur, F., Hoeveler, A., Couez, D., Barad, M., Malissen, B., Schmitt-Verhulst, A. M., and Boyer, C. 1992. Role of CD38 in surface expression of the TCR/CDδ complex and in activation for killing analyzed with a CD3δ-negative cytotoxic T lymphocyte variant. J. Immunol. 148:657–664.
Geisler, C. 1992. Failure to synthesize the CD3-gamma chain—Consequences for T cell antigen receptor assembly, processing, and expression. J. Immunol. 148:2437–2445.
Baniyash, M., Hsu, V. W., Seidin, M. F., and Klausner, R. D. 1989. The isolation and characterization of the murine T cell antigen receptor zeta chain gene. J. Biol. Chem. 264:13252–13257.
Clayton, L. K., D’Adamio, L., Howard, F. D., Sieh, M., Hussey, R. E., Koyasu, S., and Reinherz, E. L. 1991. CD3 eta and CD3 zeta are alternatively spliced products of a common genetic locus and are transcriptionally and/or post-transcriptionally regulated during T-cell development. Proc. Natl. Acad. Sci. USA 88:5202–5206.
Ohno, H., and Saito, T. 1990. CD3 zeta and eta chains are produced by alternative splicing from a common gene. Int. Immunol. 2:1117–1119.
Clayton, L. K., Diener, A. C., Lerner, A., Tse, A. G., Koyasu, S., and Reinherz, E. L. 1992. Differential regulation of T-cell receptor processing and surface expression affected by CD3 theta, an alternatively spliced product of the CD3 zeta/eta gene locus. J. Biol. Chem. 267:26023–26030.
Klausner, R. D., and Samelson, L. E. 1991. T cell antigen receptor activation pathways: The tyrosine kinase connection. Cell 64:875–878.
Frank, S. J., Niklinska, B. B., Orloff, D. G., Mercep, M., Ashwell, J. D., and Klausner, R. D. 1990. Structural mutations of the T cell receptor zeta chain and its role in T cell activation. Sciene 249:174–177.
Malissen, B., and Schmitt-Verhulst, A. M. 1993. Transmembrane signaling through the T-cell-receptor-CD3 complex. Curr. Opin. Immunol. 5:324–330.
Malissen, M., Gillet, A., Rocha, B., Trucy, J., Vivier, E., Boyer, C., Kontgen, F., Brun, N., Mazza, G., Spanopoulou, E., Guy-Grand, D., and Malissen, B. T. 1993. T cell development in mice lacking the CD3-zeta/eta gene. EMBO J. 12:4347–4355.
Aoe, T., Goto, S., Ohno, H., and Saito, T. 1994. Different cytoplasmic structure of the CD3 zeta family dimer modulates the activation signal and function of T cells. Int. Immunol. 6:1671–1679.
Klausner, R. D., Lippincott-Schwartz, J., and Bonifacino, J. S. 1990. The T cell antigen receptor: Insights into organelle biology. Annu. Rev. Cell Biol. 6:403–431.
Bonifacino, J. S., Suzuki, C. K., Lippincott-Schwartz, J., Weissman, A. M., and Klausner, R. D. 1989. Pre-Golgi degradation of newly synthesized T-cell antigen receptor chains: Intrinsic sensitivity and the role of subunit assembly. J. Cell Biol. 109:73–83.
Sussman, J. J., Bonifacino, J. S., Lippincott-Schwartz, J., Weissman, A. M., Saito, T., Klausner, R. D., and Ashwell, J. D. 1988. Failure to synthesize the T cell CD3-zeta chain: Structure and function of a partial T cell receptor complex. Cell 52:85–95.
Ono, S., Ohno, H., and Saito, T. 1995. Rapid turnover of the CD3 zeta chain independent of the TCR-CD3 complex in normal T cells. Immunity 2:639–644.
Sancho, J., Peter, M. E., Franco, R., Danielian, S., Kang, J. S., Fagard, R., Woods, J., Reed, J. C., Kamoun, M., and Terhorst, C. 1993. Coupling of GTP-binding to the T cell receptor (TCR) zeta-chain with TCR-mediated signal transduction. J. Immunol. 150:3230–3242.
Peter, M. E., Hall, C., Ruehlmann, A., Sancho, J., and Terhorst, C. 1992. The T-cell receptor zeta chain contains a GTP/GDP binding site. EMBO J. 11:933–941.
Peter, M. E., Wileman, T., and Terhorst, C. 1993. Covalent binding of guanine nucleotides to the CD3-gamma chain of the T cell receptor/CD3 complex. Eur. J. Immunol. 23:461–466.
Exley, M., Varticovski, L., Peter, M., Sancho, J., and Terhost, C. 1994. Association of phosphatidylinositol 3 kinase with a specific sequence of the T cell receptor zeta chain is dependent on T cell activation. J. Biol. Chem. 269:15140–15146.
Leahy, D. J. 1995. A structural view of CD4 and CD8. FASEB J. 9:17–25.
Parnes, J. R. 1988. Molecular biology and function of CD4 and CD8. Adv. Immunol. 44:265–311.
Janeway, C. A., Jr. 1989. The role of CD4 in T-cell activation; accessory molecule or co-receptor? Immunol. Today 10:234–238.
Ryu, S. E., Kwong, P. D., Truneh, A., Porter, T. G., Arthos, J., Rosenberg, M., Dai, X., Xuong, N., Axel, R., Sweet, R. W., and Hendrickson, W. A. 1990. Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature 348:419–426.
Wang, J., Yan, Y., Garrett, T. P. J., Liu, J., Rodgers, D. W., Garlick, R. L., Tarr, G. E., Husain, Y., Reinherr, E. L., and Harrison, S. C. 1990. Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains. Nature 348:411–418.
Arthos, J., Deen, K. C., Chaikin, M. A., Fornwald, J. A., Sathe, G., Sattentau, Q. J., Clapham, P. R., Weiss, R. A., McDougal, J. S., Pietropaolo, C., Axel, R., Truneh, A., Maddon, P. J., and Sweet, R. W. 1989. Identification of the residues in human CD4 critical for the binding of HIV. Cell 57:469–481.
Robey, E., and Axel, R. 1990. CD4: Collaborator in immune recognition and HIV infection. Cell 60:697–700.
Fleury, S., Lamarre, D., Meloche, S., Ryu, S. E., Cantin, D., Hendrickson, W. A., and Sekaly, R. P. 1991. Mutational analysis of the interaction between CD4 and class II MHC: Class II antigens contact CD4 on a surface opposite the gp 120 binding site. Cell 66:1037–1049.
Vignali, D. A., Moreno, J., Schiller, D., and Hammerling, G. J. 1992. Species-specific binding of CD4 to the beta 2 domain of major histocompatibility complex class II molecules. J. Exp. Med. 175:925–932.
Veillette, A., Bookman, M. A., Horak, E. M., and Bolen, J. B. 1988. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell 55:301–310.
Veillette, A., and Davidson, D. 1992. Src-related protein tyrosine kinase and T cell receptor signaling. Trends Genet. 8:61–66.
Criado, G., Feito, M. J., and Rojo, J. M. 1996. CD4-dependent and CD4-independent association of protein-tyrosine kinases to the T-cell receptor/CD3 complex of CD4(+) mouse T-lymphocytes. Eur. J. Immunol. 26:1228–1234.
Thome, M., Duplay, P., Guttinger, M., and Acuto, O. 1995. Syk and ZAP-70 mediate recruitment of p56lck/CD4 to the activated T-cell receptor/CD3/zeta complex. J. Exp. Med. 181:1997–2006.
Baldari, C. T., Disomma, M. M., Milia, E., Bergman, M., and Telford, J. L. 1995. Interactions between the tyrosine kinases p56lck, p59fyn and p50csk in CD4 signaling in T-cells. Eur. J. Immunol. 25:919–925.
Glaichenhaus, N., Shastri, N., Littman, D. R., and Turner, J. M. 1991. Requirements for association of p56lck with CD4 in antigen-specific signal transduction in T cells. Cell 64:511–520.
Collins, T. L., Uniyal, S., Shin, J., Strominger, J. L., Mittler, R. S., and Burakoff, S. J. 1992. p56lck association with CD4 is required for the interaction between CD4 and the TCR/CD3 complex and for optimal antigen stimulation. J. Immunol. 148:2159–2162.
Konig, R., Shen, X. L., and Germain, R. N. 1995. Involvement of both major histocompatibility complex class-II alpha-chains and beta-chains in CD4 function indicates a role for ordered oligomerization in T-cell activation. J. Exp. Med. 182:779–787.
Baldari, C. T., Milia, E., Disomma, M. M., Baldoni, F., Valitutti, S., and Telford, J. L. 1995. Distinct signaling properties identify functionally different CD4 epitopes. Eur. J. Immunol. 25:1843–1850.
Shin, J., Doyle, C., Yang, Z., Kappes, D., and Strominger, J. L. 1990. Structural features of the cytoplasmic region of CD4 required for internalization. EMBO J. 9:425–434.
Rudd, C. E. 1990. CD4, CD8 and the TCR-CD3 complex: A novel class of protein-tyrosine kinase receptor. Immunol. Today 11:400–406.
Harris, M. P. G., and Neil, J. C. 1994. Myristoylation-dependent binding of HIV-1 NEF to CD4. J. Mol. Biol. 241:136–142.
Aiken, C., Krause, L., Chen, Y. L., and Trono, D. 1996. Mutational analysis of HIV-1 NEF—Identification of 2 mutants that are temperature-sensitive for CD4 down-regulation. Virology 217:293–300.
Bandres, J. C., Shaw, A. S., and Ratner, L. 1995. HIV1 NEF protein down-regulation of CD4 surface expression—Relevance of the LCK binding domain of CD4. Virology 207:338–341.
Garcia, J. V., and Miller, A. D. 1991. Serine phosphorylation-independent downregulation of cell surface CD4 by NEF. Nature 350:508–511.
Collette, Y., Dutartre, H., Benziane, A., Ramosmorales, F., and Benarous, R. 1996. Physical and functional interaction of NEF with LCK—HIV-1 NEF-induced T-cell signaling defects. J. Biol. Chem. 271:6333–6341.
Camerini, D., and Seed, B. A. 1990. A CD4 domain important for HIV-mediated syncytium formation lies outside the virus binding site. Cell 60:747–754.
Moebius, U., Clayton, L. K., Abraham, S., Harrison, S. C., and Reinherz, E. L. 1992. The human immunodeficiency virus GP120 binding site on CD4: Delineation by quantitative equilibrium and kinetic-binding studies of mutants in conjunction with a high-resolution CD4 atomic structure. J. Exp. Med. 176:507–517.
Maddon, P. J., Dalgleish, A. G., McDougal, J. S., Clapham, P. R., Weiss, R. A., and Axel, R. 1986. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 47:333–348.
Klatzmann, D., Champagne, E., Chamaret, S., Gruest, J., Guetard, D., Hercend, T., Gluckman, J. C., and Montagnier, L. 1984. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312:767–768.
Dalgleish, A. G., Beverley, P. C., Clapham, P. R., Crawford, D. H., Greaves, M. F., and Weiss, R. A. 1984. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312:763–767.
Swain, S. L. 1983. T cell subsets and recognition of MHC class. Immunol. Rev. 74:129–142.
von Boehmer, H., Kisielow, P., Kishi, H., Scott, B., Borgulya, P., and Teh, H. S. 1989. The expression of CD4 and CD8 accessory molecules on mature T cells is not random but correlates with the specificity of the alpha beta receptor for antigen. Immunol. Rev. 109:143–151.
Johnson, P., and Williams, A. L. 1986. Striking similarities between antigen receptor J pieces and sequence in the second chain of the murine CD8 antigen. Nature 323:74–76.
Parrott, D. M. V., Tail, C., MacKenzie, S., Mowat, A., Davies, M. D., and Micklem, H. S. 1983. Analysis of the effector functions of different populations of mucosal lymphocytes. Ann. N.Y. Acad. Sci. 409:307–320.
Ratnofsky, S. E., Peterson, A., Greenstain, J. L., and Burakoff, S. J. 1987. Expression and function of CD8 in a murine T cell hybridoma. J. Exp. Med. 166:1747–1757.
Letourneur, F., Gabert, J., Cosson, P., Blanc, D., Davoust, J., and Malissen, B. A. 1990. A signaling role for the cytoplasmic segment of the CD8 alpha chain detected under limiting stimulatory conditions. Proc. Natl. Acad. Sci. USA 87:2339–2343.
Miceli, M. C., von Hoegen, P., and Parnes, J. R. 1991. Adhesion versus coreceptor function of CD4 and CD8: Role of the cytoplasmic tail in coreceptor activity. Proc. Natl. Acad. Sci. USA 88:2623–2627.
Salter, R. D., Benjamin, R. J., Wesley, P. K., Buxton, S. E., Garrett, T. P. J., Clayberger, C., Krensky, A. M., Norment, A. M., Littman, D. R., and Parham, P. 1990. A binding site for the T-cell co-receptor CD8 on the a3 domain of HLA-2. Nature 345:41–46.
Connolly, J. M., Hansen, T. H., Ingold, A. L., and Potter, T. A. 1990. Recognition by CD8 on cytotoxic T lymphocytes is ablated by several substitutions in the class I alpha 3 domain: CD8 and the T-cell receptor recognize the same class I molecule. Proc. Natl. Acad. Sci. USA 87:2137–2141.
Zamoyska, R., Derham, P., Gorman, S.D., von Hoegen, P., Bolen, J. B., Veillette, A., and Parnes, J. R. 1989. Inability of CD8 alpha polypeptides to associate with p56lck correlates with impaired function in vitro and lack of expression in vivo. Nature 342:278–281.
Aldrich, C. J., Hammer, R. E., Jones-Youngblood, S., Koszinowski, U., Hood, L., Stroynowski, I., and Forman, J. 1991. Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the alpha 3 domain of MHC I molecules. Nature 352:718–721.
Ingold, A. L., Landel, C., Knall, C., Evans, G. A., and Potter, T. A. 1991. Co-engagement of CD8 with the T cell receptor is required for negative selection. Nature 352:721–728.
Killeen, N., Moriarty, A., Teh, H. S., and Littman, D. R. 1992. Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells. J. Exp. Med. 176:89–97.
Ramsdell, F., and Fowlkes, B. J. 1989. Engagement of CD4 and CD8 accessory molecules is required for T cell maturation. J. Immunol. 143:1467–1477.
Zuniga Pflucker, J. C., Jones, L. A., Longo, D. L., and Kruisbeek, A. M. 1990. CD8 is required during positive selection of CD4-/CD8 + T cells. J. Exp. Med. 171:427–437.
Fung-Leung, W. P., Schilham, M. W., Rahemtulla, A., Kundig, T. M., Vollenweider, M., and Potter, J. 1991. CD8 is needed for development of cytotoxic T cells but not helper T cells. Cell 65:443–449.
Norment, A. M., Salter, R. D., Parham, P., Engelhard, V. H., and Littman, D. R. 1988. Cell-cell adhesion mediated by CD8 and MHC class I molecules. Nature 336:79–81.
Potter, T. A., Rajan, T. V., Dick, R. F., and Bluestone, J. A. 1989. Substitution at residue 227 of H-2 class I molecules abrogates recognition by CD8-dependent, but not CD8-independent, cytotoxic T lymphocytes. Nature 337:73–79.
Salter, R. D., Norment, A. M., Chen, B. P., Clayberger, C., Krensky, A. M., Littman, D. R., and Parham, P. 1989. Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8. Nature 338:345–347.
Turner, J. M., Brodsky, M. H., Irving, B. A., Levin, S. D., Perlmutter, R. M., and Littman, D. R. 1990. Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell 60:755–765.
Linsley, P. S., and Ledbetter, J. A. 1993. The role of the CD28 receptor during T cell responses to antigen. Annu. Rev. Immunol. 11:191–212.
June, C. H., Ledbetter, J. A., Linsley, P. S., and Thompson, C. B. 1990. Role of the CD28 receptor in T cell activation. Immunol. Today 11:211–216.
Shahinian, A., Pfeffer, K., Lee, K. P., Kundig, T. M., Kishihara, K., Wakeham, A., Kawai, K., Ohashi, P. S., Thompson, C. B., and Mak, T. W. 1993. Differential T cell costimulatory requirements in CD28-deficient mice. Science 261:609–212.
Gross, J. A., St. John, T., and Allison, J. P. 1990. The murine homologue of the T lymphocyte antigen CD28. Molecular cloning and cell surface expression. J. Immunol. 144:3201–3210.
Gross, J. A., Callas, E., and Allison, J. P. 1992. Identification and distribution of the costimulatory receptor CD28 in the mouse. J. Immunol. 149:380–388.
Turka, L. A., Ledbetter, J. A., Lee, K., June, C. H., and Thompson, C. B. 1990. CD28 is an inducible T cell surface antigen that transduces a proliferative signal in CD3+ mature thymocytes. J. Immunol. 144:1646–1653.
Liu, Y., and Linsley, P. S. 1992. Costimulation of T-cell growth. Curr. Opin. Immunol. 4:265–270.
Peach, R. J., Bajorath, J., Naemura, J., Leytze, G., Greene, J., Aruffo, A., and Linsley, P. S. 1995. Both extracellular immunoglobin-like domains of CD80 contain residues critical for binding T cell surface receptors CTLA-4 and CD28. J. Biol. Chem. 270:21181–21187.
Freeman, G. J., Gribben, J. G., Boussiotis, V. A., Ng, J. W., Restivo, J. A., Jr., Lombard, L. A., Gray, G. S., and Nadler, L. M. 1993. Cloning of B7-2: A CTLA-4 counter-receptor that costimulates human T cell proliferation. Science 262:909–911.
Lanier, L. L., O’Fallon, S., Somoza, C., Phillips, J. H., Linsley, P. S., Okumura, K., Ito, D., and Azuma, M. 1995. CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production and generation of CTL. J. Immunol. 154:97–105.
Hathcock, K. S., Laszlo, G., Pucillo, C., Linsley, P., and Hoedes, R. J., Comparative analysis of B7-1 and B7-2 costimulatory ligands: Expression and function. J. Exp. Med. 180:631–640.
Prasad, K. V., Cai, Y. C., Raab, M., Duckworth, B., Cantley, L., Shoelson, S. E., and Rudd, C. E. 1994. T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase by a cytoplasmic Tyr(P)-Met-Xaa-Met motif. Proc. Null. Acad. Sci. USA 91:2834–2838.
Lu, Y., Phillips, C. A., Bjorndahl, J. M., and Trevillyan, J. M. 1994. CD28 signal transduction: Tyrosine phosphorylation and receptor association of phosphoinositide-3 kinase correlate with Ca2+-independent costimulatory activity: Eur. J. Immunol. 24:2732–2739.
Crooks, M. E. C., Littman, D. R., Carter, R. H., Fearon, D. T., Weiss, A., and Stein, P. H. 1995. CD28-mediated costimulation in the absence of phosphatidylinositol 3-kinase association and activation. Mol. Cell. Biol. 15:6820–6828.
Kundig, T. M., Shahinian, A., Kawai, K., Mittrucker, H. W., Sebzda, E., Bachmann, M. F., Mak, T. W., and Onashi, P. S. 1996. Duration of TCR stimulation determines costimulatory requirement of T-cells. Immunity 5:41–52.
Harding, F. A., McArthur, J. G., Gross, J. A., Raulet, D. H., and Allison, J. P. 1992. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 356:607–609
Linsley, P. S., Brady, W., Grosmaire, L., Aruffo, A., Damle, N. K., and Ledbetter, J. A. 1991. Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J. Exp. Med. 173:721–730.
Schwartz, R. H. 1996. Models of T-cell anergy—Is there a common molecular mechanism? J. Exp. Med. 184:1–8.
McArthur, J. G., and Raulet, D. H. 1993. CD28-induced costimulation of T helper type 2 cells mediated by induction of responsiveness to interleukin 4. J. Exp. Med. 178:1645–1653.
Thompson, C. B., Lindsten, T., Ledbetter, J. A., Kunkel, S. L., Young, H. A., Emerson, S. G., Leiden, J. M., and June, C. H. 1989. CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc. Natl. Acad. Sci. USA 86:1333–1337.
Koulova, L., Clark, E. A., Shu, G., and Dupont, B. 1991. The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T cells. J. Exp. Med. 173:759–762.
Damle, N. K., Klussman, K., Linsley, P. S., and Aruffo, A. 1992. Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and VCAM-1 on resting and antigen-primed CD4+ T lymphocyte. J. Immunol. 148:1985–1992.
Corry, D. B., Reiner, S. L., Linsley, P. S., and Locksley, R. M. 1994. Differential effects of blockade of CD28-B7 on the development of Th1 or Th2 effector cells in experimental leishmaniasis. J. Immunol. 153:4142–4148.
Seder, R. A., Germain, R. N., Linsley, P. S., and Paul, W. E. 1994. CD28-mediated costimulation of interleukin 2 (IL-2) production plays a critical role in T cell priming for IL-4 and interferon gamma production. J. Exp. Med. 179:299–304.
King, C. L., Stupi, R. J., Craighead, N., June, C. H., and Thyphronitis, G. 1995. CD28 activation promotes Th2 subset differentiation by human CD4+ cells. Eur. J. Immunol. 25:1237–1241.
van der Pouw-Kraan, T., Van Kooten, C., Rensink, I., and Aarden, L. 1992. Interleukin (IL)-4 production by human T cells: Differential regulation of IL-4 vs. IL-2 production. Eur. J. Immunol. 22:1237–1241.
Smith, K. A. 1988. The interleukin 2 receptor. Adv. Immunol. 42:165–179.
Schwartz, R. H. 1992. Costimulation of T lymphocytes: The role of CD28, CTLA-4, and B7/BB1 in interleukin-1 production and immunotherapy. Cell 71:1065–1068.
Ohashi, Y., Takeshita, T., Nagata, K., Mori, S., and Sugamura, K. 1989. Differential expression of the IL-2 receptor subunits, p55 and p75 on various populations of primary peripheral blood mononuclear cells. J. Immunol. 143:3548–3555.
Kang, S. M., Beverly, B., Tran, A. C., Brorson, K., Schwartz, R. H., and Lenardo, M. J. 1992. Transactivation by AF-1 is a molecular target of T cell cloning anergy. Science 257:1134–1138.
Otten, G. R., and Germain, R. N. 1991. Split anergy in a CD8+ T cell: Receptor-dependent cytolysis in the absence of interleukin-2 production. Science 251:1228–1231.
Raulet, D. H. 1985. Expression and function of interleukin-2 receptors on immature thymocytes. Nature 314:101–103.
Ceredig, R., Lynch, F., and Newman, P. 1987. Phenotypic properties, interleukin 2 production, and developmental origin of a “mature” subpopulation of Lyt-2-L3T4-mouse thymocytes. Proc. Natl. Acad. Sci. USA 84:8578–8582.
Ceredig, R., Lowenthal, J. W., Nabholz, M., and MacDonald, H. R. 1985. Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells. Nature 314:98–100.
von Boehmer, H., Crisanti, A., Kisielow, P., and Haas, W. 1985. Absence of growth by most receptorexpressing fetal thymocytes in the presence of interleukin-2. Nature 314:539–540.
Zuniga Pfluecker, J. C., Smith, K. A., Tentori, L., Pardoll, D. M., Longo, D. L., and Kruisbeek, A. M. 1990. Are the IL-2 receptors expressed in the murine fetal thymus functional? Dev. Immunol. 1:59–66.
Jenkinson, E. J., Kingston, R., and Owen, J. J. 1987. Importance of IL-2 receptors in intrathymic generation of cells expressing T-cell receptors. Nature 329:160–162.
Tentori, L., Longo, D. L., Zuniga Pfluecker, J. C., Wing, C., and Kruisbeek, A. M. 1988. Essential role of the interleukin-2 receptor pathway in thymocyte maturation in vivo. J. Exp. Med. 168:1741–1747.
Kundig, T. M., Schorle, H., Bachmann, M. F., Hengartner, H., Zinkernagel, R. M., and Horak, I. 1993. Immune responses in interleukin-2-deficient mice. Science 262:1059–1061.
Schorle, H., Holtschke, T., Hunig, T., Schimpl, A., and Horak, I. 1991. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature 352:621–624.
Sadlack, B., Merz, H., Schorle, H., Schimpl, A., Feller, A. C., and Horak, I. 1993. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 75:253–261.
Suzuki, H., Kundig, T. M., Furlonger, C., Wakeham, A., Timms, E., Matsuyama, T., Schmits, R., Simard, J. J. L., Ohashi, P. S., Griesser, H., Taniguchi, T., Paige, C. J., and Mak, T. W. 1995. Deregulated T-cell activation and autoimmunity in mice lacking interleukin-2 receptor-beta. Science 268:1472–1476.
Ma, A., Datta, M., Margosian, E., Chen, J. Z., and Horak, I. 1995. T-cells, but not B-cells, are required for bowel inflammation in interleukin 2-deficient mice. J. Exp. Med. 182:1567–1572.
Simpson, S. J., Mizoguchi, E., Allen, D., Bhan, A. K., and Terhorst, C. 1995. Evidence that CD4(+), but not CD8(+) T-cell are responsible for murine interleukin-2-deficient colitis. Eur. J. Immunol. 25:2618–2625.
Hatakeyama, M., Kono, T., Kobayashi, N., Kawahara, A., Levin, S. D., Perlmutter, R. M., and Taniguchi, T. 1991. Interaction of the IL-2 receptor with the src-family kinase p56lck: Identification of novel intermolecular association. Science 252:1523–1528.
Minami, Y., Kono, T., Miyazaki, T., and Taniguchi, T. 1993. The IL-2 receptor complex: Its structure, function, and target genes. Annu. Rev. Immunol. 11:245–268.
Evans, G. A., Goldsmith, M. A., Johnston, J. A., Xu, W. D., Weiler, S. R., Erwin, R., Howard, O. M. Z., Abraham, R. T., O’Shea, J. J., Greene, W. C., and Farrar, W. L. 1995. Analysis of interleukin-2-dependent signal-transduction through the SHC/GRB2 adapter pathway—Interleukin-2-dependent mitogenesis does not require SHC phosphorylation or receptor association. J. Biol. Chem. 270:28858–28863.
Kirken, R. A., Rui, H., Malabarba, M. G., Howard, O. M., Kawamura, M., O’Shea, J. J., and Farrar, W. L. 1995. Activation of JAK3, but not JAK1, is critical for IL-2 induced proliferation and STATS recruitment by a COOH-terminal region of the IL-2 receptor beta-chain. Cytokine 7:689–700.
Rayter, S. I., Woodrow, M., Lucas, S. C., Cantrell, D. A., and Downward, J. 1992. p21ras mediates control of IL-2 gene promoter function in T cell activation. EMBO J. 11:4549–4556.
Woodrow, M., Rayter, S., Downward, J., and Cantrell, D. A. 1993. p21ras function is important for T cell antigen receptor and protein kinase C regulation of nuclear factor of activated cells. J. Immunol. 150:1–9.
Fields, P. E., Gajewski, T. F., and Fitch, F. W. 1996. Blocked ras activation in anergic CD4+ T-cells. Science 271:1276–1278.
Su, B., Estela, J., Hibi, M., Kallunki, T., Karin, M., and Ben-Neriah, Y. 1994. JNK is involved in signal integration during costimulation of T lymphocytes. Cell 77:727–736.
Izquierdo, M., Leevers, S. J., Marshall, C. J., and Cantrell, D. 1993. p21ras couples the T cell antigen receptor to extracellular signal-regulated kinase 2 in T lymphocytes. J. Exp. Med. 178:1199–1208.
Izquierdo, M., Leevers, S. J., Williams, D. H., Marshall, C. J., Weiss, A., and Cantrell, D. 1994. The role of protein kinase C in the regulation of extracellular signal-regulated kinase by the T cell antigen receptor. Eur. J. Immunol. 24:2462–2468.
Sundstedt, A., Sigvardsson, M., Leanderson, T., Hedlund, G., and Dohlsten, M. 1996. In-vivo anergized CD4+ T-cells express perturbed AP-1 and NF-kappa-B transcription factors. Proc. Natl. Acad. Sci. USA 93:979–984.
Becker, J. C., Brabletz, T., Kirchner, T., Conrad, C. T., and Brocker, E. B. 1995. Negative transcriptional regulation in anergic T-cells. Proc. Natl. Acad. Sci. USA 92:2375–2378.
Jain, J., Loh, C., and Rao, A. 1995. Transcriptional regulation of the IL-2 gene. Curr. Opin. Immunol. 7:333–342.
Pingel, J. T., and Thomas, M. L. 1989. Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. Cell 58:1055–1065.
Weiss, A., Irving, B. A., Tan, L. K., and Koretzky, G. A. 1991. Signal transduction by the T cell antigen receptor. Semin. Immunol. 3:313–324.
Koretzky, G. A., Picus, J., Thomas, M. L., and Weiss, A. 1990. Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway. Nature 346:66–68.
Fischer, E. H., Charbonneau, H., and Tonks, N. K. 1991. Protein tyrosine phosphatases: A diverse family of intracellular and transmembrane enzymes. Science 253:401–406.
Trowbridge, I. S., and Thomas, M. L. 1994. CD45: An emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development. Annu. Rev. Immunol. 12:85–116.
Chan, A. C., Desai, D. M., and Weiss, A. 1994. The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. Annu. Rev. Immunol. 12:555–592.
Koretzky, G. A., Kohmetscher, M. A., Kadleck, T., and Weiss, A. 1992. Restoration of T cell receptormediated signal transduction by transfection of CD45 cDNA into a CD45-deficient variant of the Jurkat T cell line. J. Immunol. 149:1138–1142.
Shiroo, M., Goff, L., Biffen, M., Shivnan, E., and Alexander, D. 1992. CD45 tyrosine phosphataseactivated P59FYN couples the T cell antigen receptor to pathways of diacylglycerol production, protein kinase C activation and calcium influx. EMBO J. 11:4887–4897.
Kishihara, K., Penninger, J., Wallace, V. A., Kundig, T. M., Kawai, K., Wakeham, A., Timms, E., Pfeffer, K., Ohashi, P. S., Thomas, M. L., Furlonger, C., Paige, C. J., and Mak, T. W. 1993. Normal B lymphocyte development but impaired T cell maturation in CD45-exon 6 protein tyrosinc phosphatase-deficient mice. Cell 74:143–156.
Cyster, J. G., Healy, J. I., Kishihara, K., Mak, T. W., Thomas, M. L., and Goodnow, C. C. 1996. Regulation of B-lymphocyte negative and positive selection of tyrosine phosphatase CD45. Nature 381:325–328.
Akbar, A. N., Terry, L., Timms, A., Beverley, P. C., and Janossy, G. 1988. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J. Immunol. 140:2171–2178.
Yamada, A., Kaneyuki, T., Hara, A., Rothstein, D. M, and Yokoyama, M. M. 1992. CD45 isoform expression in human neonatal T cells: Expression and turnover of CD45 isoforms on neonatal versus adult T cells after activation. Cell. Immunol. 142:114–124.
Fujii, Y., Okumura, M., Inada, K., and Nakahara, K. 1992. Reversal of CD45R isoform switching in CD8 + T cells. Cell. Immunol. 139:176–184.
Sanders, M. E., Makgoba, M. W., Sharrow, S. O., Stephany, D., Springer, T. A., Young, H. A., and Shaw, S. 1988. Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J. Immunol. 140:1401–1407.
Gray, D. 1993. Immunological memory. Annu. Rev. Immunol. 11:49–77.
Rogers, P. R., Pilapil, S., Hayakawa, K., Romain, P. L., and Parker, D. C. 1992. CD45 alternative exon expression in murine and human CD4+ T cell subsets. J. Immunol. 148:4054–4065.
Lee, W. T., and Vitetta, E. S. 1992. Changes in expression of CD45R during the development of Th1 and Th2 cell lines. Eur. J. Immunol. 22:1455–1459.
Beverley, P. C., Daser, A., Michie, C. A., and Wallace, D. L. 1992. Functional subsets of T cells defined by isoforms of CD45. Biochem. Soc. Trans. 20:184–187.
Smith, S. H., Brown, M. H., Rowe, D., Callard, R. E., and Beverley, P. C. 1986. Functional subsets of human helper-inducer cells defined by a new monoclonal antibody, UCHL1. Immunology 58:63–70.
Mason, D. 1992. Subsets of CD4+ T cells defined by their expression of different isoforms of the leucocyte-common antigen, CD45. Biochem. Soc. Trans. 20:188–190.
Birkeland, M. L., Kraus, T., Tardelli, L., and Pure, E. 1992. Progressive changes in CD45RB phenotype and lymphokine production by murine CD4+ T cells after alloantigen exposure. Immunology 75:632–638.
Stamenkovic, I., Sgroi, D., Aruffo, A., Sy, M. S., and Anderson, T. 1991. The B lymphocyte adhesion molecule CD22 interacts with leukocyte common antigen CD45RO on T cells and alpha 2–6 sialyltransferase, CD75, on B cells. Cell 66:1133–1144.
Aruffo, A., Kanner, S. B., Sgroi, D., Ledbetter, J. A., and Stamenkovic, I. 1992. CD22-mediated stimulation of T cells regulates T-cell receptor/CD3-induced signaling. Proc. Natl. Acad. Sci. USA 89:10242–10246.
Schraven, B., Samstag, Y., Altevogt, P., and Meuer, S. C. 1990. Association of CD2 and CD45 on human T lymphocytes. Nature 345:71–74.
Volarevic, S., Niklinska, B. B., Burns, C. M., June, C. H., Weissman, A. M., and Ashwell, J. D. 1993. Regulation of TCR signaling by CD45 lacking transmembrane and extracellular domains. Science 260:541–544.
Desai, D. M., Sap, J., Schlessinger, J., and Weiss, A. 1993. Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase. Cell 73:541–554.
Desai, D. M., Sap, J., Silvennoinen, O., Schlessinger, J., and Weiss, A. 1994. The catalytic activity of the CD45 membrane-proximal phosphatase domain is required for TCR signaling and regulation. EMBO J. 13:4002–4010.
Hovis, R. R., Donovan, J. A., Musci, M. A., Motto, D. G., Goldman, F. D., Ross, S. E., and Koretzky, G. A. 1993. Rescue of signaling by a chimeric protein containing the cytoplasmic domain of CD45. Science 260:544–546.
Niklinska, B. B., Hou, D., June, C., Weissman, A. M., and Ashwell, J. D. 1994. CD45 tyrosine phosphatase activity and membrane anchoring are required for T-cell antigen receptor signaling. Mol. Cell. Biol. 14:8078–8084.
Duplay, P., Alcover, A., Fargeas, C., Sekaly, R. P., and Branton, P. E. 1996. An activated epidermal growth-factor receptor/LCK chimera restores early T-cell receptor-mediated calcium response in a CD45-deficient T-cell line. J. Biol. Chem. 271:17896–17902.
Burns, C. M., Sakaguchi, K., Appella, E., and Ashwell, J. D. 1994. CD45 regulation of tyrosine phosphorylation and enzyme activity of src family kinases. J. Biol. Chem. 269:13594–13600.
McFarland, E. D., Hurley, T. R., Pingel, J. T., Sefton, B. M., Shaw, A., and Thomas, M. L. 1993. Correlation between SRC family member regulation by the protein-tyrosine-phosphatase CD45 and transmembrane signaling through the T-cell receptor. Proc. Natl. Acad. Sci. USA 90:1402–1406.
Hurley, T. R., Hyman, R., and Sefton, B. M. 1993. Differential effects of expression of the CD45 tyrosine protein phosphatase on the tyrosine phosphorylation of the LCK, FYN, and c-SRC tyrosine protein kinases. Mol. Cell. Biol. 13:1651–1656.
Ostergaard, H. L., and Trowbridge, I. S. 1990. Coclustering CD45 with CD4 or CD8 alters the phosphorylation and kinase activity of p56lck. J. Exp. Med. 172:347–350.
Mustelin, T., Pessa Morikawa, T., Autero, M., Gassmann, M., Andersson, L. C., Gahmberg, C. G., and Burn, P. 1992. Regulation of the p59fyn protein tyrosine kinase by the CD45 phosphotyrosine phosphatase. Eur. J. Immunol. 22:1173–1178.
Mustelin, T., Coggeshall, K. M., and Altman, A. 1989. Rapid activation of the T-cell tyrosine protein kinase pp56lck by the CD45 phosphotyrosine phosphatase. Proc. Natl. Acad. Sci. USA 86:6302–6306.
Ostergaard, J. L. 1988. Expression of CD45 alters phosphorylation of the lck-encoded tyrosine protein kinase in murine lymphoma T cell lines. Proc. Natl. Acad. Sci. USA 85:4232–4236.
Brunet, J. F., Denizot, F., Luciani, M. F., Roux Dosseto, M., Suzan, M., Mattei, M. G., and Golstein, P. A. 1987. A new member of the immunoglobulin superfamily—CTLA-4. Nature 328:267–270.
Linsley, P. S., Greene, J. L., Tan, P., Bradshaw, J., Ledbetter, J. A., Anasetti, C., and Damle, N. K. 1992. Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J. Exp. Med. 176:1595–1604.
Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L. S., Damle, N. K., and Ledbetter, J. A. 1991. CTLA-4 is a second receptor for the B cell activation antigen B7. J. Exp. Med. 174:561–569.
Howard, T. A., Rochelle, J. M., and Seldin, M. F. 1991. CD28 and CTLA-4, two related members of the Ig supergene family, are tightly linked on proximal mouse chromosome 1. Immunogenelics 33:74–76.
Lafage Pochitaloff, M., Costello, R., Couez, D., Simonetti, J., Mannoni, P., Mawas, C., and Olive, D. 1990. Human CD28 and CTLA-4 Ig superfamily genes are located on chromosome 2 at bands q33–q34. Immunogenelics 31:198–201.
Harper, K., Balzano, C., Rouvier, E., Mattei, M. G., Luciani, M. F., and Golstein, P. 1991. CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location. J. Immunol. 147:1037–1044.
Lindsten, T., Lee, K. P., Harris, E. S., Petryniak, B., Craighead, N., Reynolds, P. J., Lombard, D. B., Freeman, G. J., Nadler, L. M., Gray, G. S., Thompson, C. B., and June, C. H. 1993. Characterization of CTLA-4 structure and expression on human T cells. J. Immunol. 151:3489–3499.
Freeman, G. J., Lombard, D. B., Gimmi, C. D., Brod, S. A., Lee, K., Laning, J. C., Hafler, D. A., Dorf, M. E., Gray, G. S., Reiser, H., June, C. H., Thompson, C. B., and Nadler, L. M. 1992. CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production. J. Immunol. 149:3795–3801.
June, C. H., Bluestone, J. A., Nadler, L. M., and Thompson, C. B. 1994. The B7 and CD28 receptor families. Immunol. Today 15:321–331.
Guinan, E. C., Gribben, J. G., Boussiotis, V. A., Freeman, G. J., and Nadler, L. M. 1994. Pivotal role of the B7-CD28 pathway in transplantation tolerance and tumor immunity. Blood 84:3261–3282.
Linsley, P. S., Nadler, S. G., Bajorath, J., Peach, R., Leung, H. T., Rogers, J., Bradshaw, J., Stebbins, M., Leytze, G., Brady, W., Malacko, A. R., Marquardt, H., and Shaw, S. Y. 1995. Binding stoichiometry of the cytotoxic T lymphocyte-associated molecule-4 (CTLA-4). A disulfide-linked homodimer binds two CD86 molecules. J. Biol. Chem. 270:15417–15424.
Kearney, E. R., Walunas, T. L., Karr, R. W., Morton, P. A., Loh, D. Y., Bluestone, J. A., and Jenkins, M. K. 1995. Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T-cells in vivo is dependent on CD28 costimulation and inhibited by CTLA-4. J. Immunol. 155:1032–1036.
Harlan, D. M., Abe, R., Lee, K. P., and June, C. H. 1995. Potential roles of the B7 and CD28 receptor families in autoimmunity and immune evasion. Clin. Immunol. Immunopathol. 75:99–111.
Linsley, P. S. 1995. Distinct roles for CD28 and cytotoxic T-lymphocyte-associated molecule-4 receptors during T-cell activation. J. Exp. Med. 182:289–292.
Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesser, H., and Mak, T. W. 1995. Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science 270:985–988.
Marengere, L. E., Waterhouse, P., Duncan, G. S., Mittrucker, H. W., Feng, G. S., and Mak, T. W. 1996. Regulation of T cell receptor signaling by tyrosine phosphatase STP association with CTLA-4. Science 272:1170–1173.
Springer, T. A., Dustin, M. L., Kishimoto, T. K., and Marlin, S. D. 1987. The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: Cell adhesion receptors of the immune system. Annu. Rev. Immunol. 5:223–252.
Makgoba, M. W., Sanders, M. E., and Shaw, S. 1989. The CD2-LFA-3 and LFA-1-ICAM-pathways relevance to T-cell recognition. Immunol. Today 10:417–422.
Springer, T. A. 1990. Adhesion receptors of the immune system. Nature 346:425–434.
Mitnacht, R., Tacke, M., and Hunig, T. 1995. Expression of cell-interaction molecules by immature rat thymocytes during passage through the CD4(+)8(+) compartment—developmental regulation and induction by T-cell receptor engagement of CD2, CD5, CD28, CD11a, CD44 and CD53. Eur. J. Immunol. 25:328–332.
Sen, J., Arceci, R. J., Jones, W., and Burakoff, S. J. 1989. Expression and ontogeny of murine CD2. Eur. J. Immunol. 19:1297–1302.
Cantley, L. C., Auger, K. R., Carpenter, C., Duckworth, B., Graziani, A., Kapeller, R., and Soltoff, S. 1991. Oncogenes and signal transduction. Cell 64:281–302.
Mentz, F., Mossalayi, M. D., Ouaaz, F., and Debre, P. 1995. Involvement of cAMP in CD3 T cell receptor complex-and CD2-mediated apoptosis of human thymocytes. Eur. J. Immunol. 25:1798–1801.
Karmann, K., Hughes, C. C. W., Fanslow, W. C., and Pober, J. S. 1996. Endothelial cells augment the expression of CD4 ligand on newly activated human CD4+ T-cells through a CD2/LFA-3 signaling pathway. Eur. J. Immunol. 26:610–617.
Osborn, L., Day, E. S., Miller, G. T., Karpusas, M., Tizard, R., and Meuer, S. C. 1995. Amino acid residues required for binding of lymphocyte function-associated antigen-3 (CD58) to its counter-receptor CD2. J Exp. Med. 181:429–434.
Murray, A. J., Lewis, S. J., Barclay, A. N., and Brady, R. L. 1995. One sequence, 2 folds—A metastable structure of CD2. Proc. Natl. Acad. Sci. USA 92:7337–7341.
Dustin, M. L., Ferguson, L. M., Chan, P. Y., Springer, T. A., and Golan, D. E. 1996. Visualization of CD2 interaction with LFA-3 and determination of the 2-dimensional dissociation-constant for adhesion receptors in a contact area. J. Cell Biol. 132:465–474.
Gollab, J. A., Li, J., Reinherz, E. L., and Ritz, J. 1995. CD2 regulates responsiveness of activated T-cells to interleukin-12. J. Exp. Med. 182:721–731.
Biancone, L., Andres, G., Ahn, H., Lim, A., Dai, C., Noelle, R., and Yagita, H. 1996. Distinct regulatory roles of lymphocyte costimulatory pathways on T-helper type 2-mediated autoimmune disease. J. Exp. Med. 183:1473–1481.
Semnani, R. T., Nutman, T. B., Hochman, P., Shaw, S., and Vanseventer, G. A. 1994. Costimulation by purified intercellular-adhesion molecule-1 and lymphocyte function-associated antigen-3 induces distinct proliferation, cytokine and cell-surface antigen profiles in human naive and memory CD4(+) T-cells. J. Exp. Med. 180:2125–2135.
Kanner, S. B., Damle, N. K., Blake, J., Aruffo, A., and Ledbetter, J. A. 1992. CD2/LFA-3 ligation induces phospholipase-C gamma 1 tyrosine phosphorylation and regulates CD3 signalling. J. Immunol. 148:2023–2029.
Koretzky, G. A., Picus, J., Schultz, T., and Weiss, A. 1991. Tyrosine phosphatase CD45 is required for T cell antigen receptor and CD2 mediated activation of a protein tyrosine kinase and interleukin 2 production. Proc. Natl. Acad. Sci. USA 88:2037–2041.
Osman, N., Ley, S. C., and Crumpton, M. J. 1992. Evidence for an association between the T cell receptor/CD3 antigen complex and the CD5 antigen in human T lymphocytes. Eur. J. Immunol. 22:2995–3000.
Davies, A. A., Ley, S. C., and Crumpton, M. J. 1992. CD5 is phosphorylated on tyrosine after stimulation of the T-cell antigen receptor complex. Proc. Natl. Acad. Sci. USA 89:6368–6372.
Vandenberghe, P., and Ceuppens, J. L. 1991. Immobilized anti-CD5 together with prolonged activation of protein kinase C induce interleukin 2-dependent T cell growth: Evidence for signal transduction through CD5. Eur. J. Immunol. 21:251–259.
Spertini, F., Stohl, W., Ramesh, N., Moody, C., and Geha, R. S. 1991. Induction of human T cell proliferation by a monoclonal antibody to CD5. J. Immunol. 146:47–52.
Indraccolo, S., Mion, M., Zamarchi, R., Coppola, V., Calderazzo, F., Amadori, A., and Chieco Bianchi, L. 1995. A CD3+CD8+ T cell population lacking CD5 antigen expression is expanded in peripheral blood of human immunodeficiency virus-infected patients. Clin. Immunol. Immunopathol. 77:253–261.
Hassan, J., Yanni, G., Hegarty, V., Feighery, C., Bresnihan, B., and Whelan, A. 1996. Increased numbers of CD5+ B cells and T cell receptor (TCR) gamma delta+ T cells are associated with younger age of onset in rheumatoid arthritis (RA). Clin. Exp. Immunol. 103:353–356.
Ragheb, S., and Lisak, R. P. 1990. The frequency of CD5+ B lymphocytes in the peripheral blood of patients with myasthenia gravis. Neurology 40:1120–1124.
Araga, S., Kishimoto, M., Adachi, A., Nakayasu, H., Takenaka, T., and Takahashi, K. 1995. The CD5+ B cells and myasthenia gravis. Auloimmunity 20:129–134.
Van de Velde, H., von Hoegen, I., Luo, W., Pames, J. R., and Thielemans, K. 1991. The B-cell surface protein CD72/Lyb-2 is the ligand for CD5. Nature 351:662–665.
Gordon, J. 1994. B-cell signaling via the C-type lectins CD23 and CD72. Immunol. Today 15:411–417.
Gruss, H. J., and Dower, S. K. 1995. Tumor-necrosis-factor ligand superfamily—Involvement in the pathology of malignant lymphomas. Blood 85:3378–3404.
Bazzoni, F., and Beutler, B. 1996. The tumor necrosis factor ligand and receptor families. N. Engl. J. Med. 334:1717–1725.
Ogasawara, J., Suda, T., and Nagata, S. 1995. Selective apoptosis of CD4+ CD8+ thymocytes by the anti-Fas antibody. J. Exp. Med. 181:485–491.
Alderson, M. R., Tough, T. W., Davis-Smith, T., Braddy, S., Falk, B., Schooley, K. A., Goodwin, R. G., Smith, C. A., Ramsdell, F., and Lynch, D. H. 1995. Fas ligand mediates activation-induced cell death in human T lymphocytes. J. Exp. Med. 181:71–77.
Crispe, I. N. 1994. Fatal interactions: Fas-induced apoptosis of mature T cells. Immunity 1:347–349.
Ju, S. T., Panka, D. J., Cui, H., Ettinger, R., el Khatib, M., Sherr, D. H., Stanger, B. Z., and Marshak Rothstein, A. 1995. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature 373:444–448.
Van Parijs, L., Ibraghimov, A., and Abbas, A. K. 1996. The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance. Immunity 4:321–328.
Griffith, T. S., Brunner, T., Fletcher, S. M., Green, D. R., and Ferguson, T. A. 1995. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 270:1189–1191.
Rieux Laucat, F., Le Deist, F., Hivroz, C., Roberts, I. A. G., Debatin, K. M., Fischer, A., and De Villartay, J. P. 1995. Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 268:1347–1351.
Bellgrau, D., Gold, D., Selawry, H., Moore, J., Franzusoff, A., and Duke, R. C. 1995. A role for CD95 ligand in preventing graft rejection. Nature 377:630–632.
Suda, T., Okazaki, T., Naito, Y., Yokota, T., Arai, N., Ozaki, S., Nakao, K., and Nagata, S. 1995. Expression of the Fas ligand in cells of T cell lineage. J. Immunol. 154:3806–3813.
Iwai, K., Miyawaki, T., Takizawa, T., Konno, A., Ohta, K., Yachie, A., Seki, H., and Taniguchi, N. 1994. Differential expression of bcl-2 and susceptibility to anti-Fas-mediated cell death in peripheral blood lymphocytes, monocytes, and neutrophils. Blood 84:1201–1208.
Brunner, T., Mogil, R. J., LaFace, D., Yoo, N. J., Mahboubi, A., Echeverri, F., Martin, S. J., Force, W. R., Lynch, D. H., Ware, C. F., and Green, D. R. 1995. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature 373:441–444.
Singer, G. G., and Abbas, A. K. 1994. The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice. Immunity 1:365–371.
Renno, T., Hahne, M., Tschopp, J., and MacDonald, H. R. 1996. Peripheral T-cells undergoing superantigen-induced apoptosis in-vivo express B220 and up-regulate fas and FAS ligand. J. Exp. Med, 183:431–437.
Rathmell, J. C., Cooke, M. P., Ho, W. Y., Grein, J., Townsend, S. E., Davis, M. M., and Goodnow, C. C. 1995. CD95 (Fas)-dependent elimination of self-reactive B cells upon interaction with CD4+ T cells. Nature 376:181–184.
Rothstein, T. L., Wang, J. K., Panka, D. J., Foote, L. C., Wang, Z., Stanger, B., Cui, H., Ju, S. T., and Marshak Rothstein, A. 1995. Protection against Fas-dependent Th1-mediated apoptosis by antigen receptor engagement in B cells. Nature 374:163–165.
Schattner, E. J., Elkon, K. B., Yoo, D. H., Tumang, J., Krammer, P. H., Crow, M. K., and Friedman, S. M. 1995. CD40 ligation induces Apo-1/Fas expression on human B lymphocytes and facilitates apoptosis through the Apo-1/Fas pathway. J. Exp. Med. 182:1557–1565.
Rensing-Ehl, A., Frei, K., Flury, R., Matiba, B., Mariani, S. M., Weller, M., Aebischer, P., Krammer, P. H., and Fontana, A. 1995. Local Fas/APO-1 (CD95) ligand-mediated tumor cell killing in vivo. Eur. J. Immunol. 25:2253–2258.
Lowin, B., Hahne, M., Mattmann, C., and Tschopp, J. 1994. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 370:650–652.
Arase, H., Arase, N., and Saito, T. 1995. Fas-mediated cytotoxicity by freshly isolated natural killer cells. J. Exp. Med. 181:1235–1238.
Kaegi, D., Vignaux, F., Ledermann, B., Buerki, K., Depraetere, V., Nagata, S., Hengartner, H., and Golstein, P. 1994. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science 265:528–530.
Rouvier, E., Luciani, M. F., and Golstein, P. 1993. Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity. J. Exp. Med. 177:195–200.
Ashany, D., Song, X., Lacy, E., Nikolic Zugic, J., Friedman, S. M., and Elkon, K. B. 1995. Th1 CD4+ lymphocytes delete activated macrophages through the Fas/APO-1 antigen pathway. Proc. Natl. Acad. Sci. USA 92:11225–11229.
Kagi, D., Ledermann, B., Burki, K., Zinkernagel, R. M., and Hengartner, H. 1996. Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in-vivo. Annu. Rev. Immunol. 14:207–232.
Suess, G., and Shortman, K. 1996. A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand-induced apoptosis. J. Exp. Med. 183:1789–1789.
Lynch, D. H., Watson, M. L., Alderson, M. R., Baum, P. R., Miller, R. E., Tough, T., Gibson, M., Davis Smith, T., Smith, C. A., Hunter, K., Bhat, D., Din, W., Goodwin, R. G., and Seldin, M. F. 1994. The mouse Fas-ligand gene is mutated in gld mice and is part of an TNF family gene cluster. Immunity 1:131–136.
Watanabe, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A., and Nagata, S. 1992. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314–316.
Westendorp, M. O., Frank, R., Ochsenbauer, C., Stricker, K., Dhein, J., Walczak, H., Debatin, K. M., and Krammer, P. H. 1995. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp 120. Nature 375:497–500.
Davignon, D., Martz, E., Reynolds, T., Kurzinger, K., and Springer, T. A. 1981. Monoclonal antibody to a novel lymphocyte function-associated antigen (LFA-1): Mechanism of blockade of T lymphocyte-mediated killing and effects on other T and B lymphocyte functions. J. Immunol. 127:590–595.
Sanchez Madrid, F., Krensky, A. M., Ware, C. F., Robbins, E., Strominger, J. L., Burakoff, S. J., and Springer, T. A. 1982. Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc. Natl. Acad. Sci. USA 79:7489–7493.
Springer, T. A. 1994. Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 76:301–314.
Springer, T. A., Davignon, D., Ho, M. K., Kuerzinger, K., Martz, E., and Sanchez Madrid, F. 1982. LFA-1 and Lyt-2,3, molecules associated with T lymphocyte-mediated killing; and Mac-1. and LFA-1 homologue associated with complement receptor function. Immunol. Rev. 68:171–195.
Starling, G. C., Mclellan, A. D., Egner, W., Sorg, R. V., Fawcett, J., Simmons, D. L., and Hart, D. N. 1995. Intercellular-adhesion molecule-3 is the predominant costimulatory ligand for leukocyte function antigen-1 on human blood dendritic cells. Eur. J. Immunol. 25:2528–2532.
Sligh, J. E., Jr., Ballantyne, C. M., Rich, S. S., Hawkins, H. K., Smith, C. W., Bradley, A., and Beaudet, A. L. 1993. Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1. Proc. Natl. Acad. Sci. USA 90:8529–8533.
Butcher, E. C. 1991. Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity. Cell 67:1033–1036.
Krensky, A. M., Sanchez Madrid, F., Robbins, E., Nagy, J. A., Springer, T. A., and Burakoff, S. J. 1983. The functional significance, distribution, and structure of LFA-1, LFA-2, and LFA-3: Cell surface antigens associated with CTL-target interactions. J. Immunol. 131:611–616.
Scheynius, A., Camp, R. L., and Pure, E. 1993. Reduced contact sensitivity reactions in mice treated with monoclonal antibodies to leukocyte function-associated molecule-1 and intercellular adhesion molecule-1. J. Immunol. 150:655–663.
Andersson, E. C., Christensen, J. P., Scheynius, A., Marker, O., and Thomsen, A. R. 1995. Lymphocytic choriomeningitis virus-infection is associated with long-standing perturbation of LFA-1 expression on CD8(+) T-celts. Scand. J. Immunol. 42:110–118.
Hamann, A., Jablonski Westrich, D., Duijvestijn, A., Butcher, E. C., Baisch, H., Harder, R., and Thiele, H. G. 1988. Evidence for an accessory role of LFA-1 in lymphocyte-high endothelium interaction during homing. J. Immunol. 140:693–699.
Camp, R. L., Scheynius, A., Johansson, C., and Pure, E. 1993. CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation. J. Exp. Med. 178:497–507.
Odum, N., Hofmann, B., Morling, N., Platz, P., Ryder, L. P., Tvede, N., Geisler, C., and Svejgaard, A. 1988. Differences between primed allogeneic T-cell responses and the primary mixed leucocyte reaction. Primed T cells become independent of the blocking effects of monoclonal antibodies against IL-1 beta and the CD5, CD11a (LFA-1), and CD11c (p 150,95) molecules. Scand. J. Immunol. 27:405–411.
Schmits, R., Kundig, T. M., Baker, D. M., Shumaker, G., Simard, J. J. L., Duncan, G., Wakeham, A., Shahinian, A., Vanderheiden, A., Bachmann, M. F., Ohashi, P. S., Mak, T. W., and Hickstein, D. D. 1996. LFA-1-deficient mice show normal CTL responses to virus but fail to reject immunogenic tumor. J. Exp. Med. 183:1415–1426.
Danilenko, D. M, Rossitto, P. V., Vandervieren, M., Letrong, H., Mcdonough, S. P., Affolter, V. K., and Moore, P. F. 1995. A novel canine leukointegrin, alpha(d)beta(2) is expressed by specific macrophage subpopulations in tissue and a minor CD8(+) lymphocyte subpopulation in peripheral blood. J. Immunol. 155:35–44.
Ingalls, R. R., and Golenbock, D. T. 1995. CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. J. Exp. Med. 181:1473–1479.
Anderson, D. C., Schmalsteig, F. C., Finegold, M. J., Hughes, B. J., Rothlein, R., Miller, L. J., Kohl, S., Tosi, M. F., Jacobs, R. L., Waldrop, T. C., Goldman, A. S., Shearer, W. T., and Springer, T. A. 1985. The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: Their quantitative definition and relation to leukocyte dysfunction and clinical features. J. Infect. Dis. 152:668–689.
Arnaout, M. A., Spits, H., Terhorst, C., Pitt, J., and Todd, R. F., III. 1984. Deficiency of a leukocyte surface glycoprotein (LFA-1) in two patients with Mo1 deficiency. Effects of cell activation on Mo1/LFA-1 surface expression in normal and deficient leukocytes. J. Clin. Invest. 74:1291–1300.
Beatty, P. G., Ochs, H. D., Harlan, J. M., Price, T. H., Rosen, H., Taylor, R. F., Hansen, J. A., and Klebanoff, S. J. 1984. Absence of monoclonal-antibody-defined protein complex in boy with abnormal leucocyte function. Lancet 1:535–537.
Buescher, E. S., Gaither, T., Nath, J., and Gallin, J. I. Abnormal adherence-related functions of neutrophils, monocytes, and Epstein-Barr virus-transformed B cells in a patient with C3bi receptor deficiency. Blood 65:1382–1390.
Carter, W. G., Ryan, M. C., and Gahr, P. J. 1991. Epilegrin, a new cell adhesion ligand for integrin (a3β1) in epithelial basement membranes. Cell 65:599–610.
Hemler, M. E. 1990. VLA proteins in the integrin family: Structures, functions, and their role on leukocytes. Annu. Rev. Immunol. 8:365–400.
Salomon, D. R., Mojcik, C. F., Chang, A. C., Wadsworth, S., Adams, D. H., Coligan, J. E., and Shevach, E. M. 1994. Constitutive activation of integrin alpha 4 beta 1 defines a unique stage of human thymocyte development. J. Exp. Med. 179:1573–1584.
Mojcik, C. F., Salomon, D. R., Chang, A. C., and Shevach, E. M. 1995. Differential expression of integrins on human thymocyte subpopulations. Blood 86:4206–4217.
Crisa, L., Cirulli, V., Ellisman, M. H., Ishii, J. K., Elices, M. J., and Salomon, D. R. 1996. Cell-adhesion and migration are regulated at distinct stages of thymic T-cell development—The roles of fibronectin, VLA4, and VLA5. J. Exp. Med. 184:215–228.
Boyd, R. L., Tucek, C. L., Godfrey, D. I., Izon, D. J., Wilson, T. J., Davidson, N. J., Bean, A. G., Ladyman, H. M., Ritter, M. A., and Hugo, P. 1993. The thymic microenvironment. Immunol. Today 14:445–459.
Damle, N. K., Klussman, K., Leytze, G., Myrdal, S., Aruffo, A., Ledbetter, J. A., and Linsley, P. S. 1994. Costimulation of T lymphocytes with integrin ligands intracellular adhesion molecule-1 or vascular cell adhesion molecule-1 induces functional expression of CTLA-4, a second receptor for B7. J. Immunol. 152:2686–2697.
Kishimoto, T. K., Larson, R. S., Corbi, A. L., Dustin, M. L., Staunton, D. E., and Springer, T. A. 1990. The leucocyte integrins. 46:149–181.
Sato, T., Tachibana, K., Nojima, Y., D’Avirro, N., and Morimoto, C. 1995. Role of the VLA-4 molecule in T cell costimulation. Identification of the tyrosine phosphorylation pattern induced by the ligation of VLA-4. J. Immunol. 155:2938–2947.
Dietsch, M. T., Chan, P. Y., Kanner, S. B., Gilliland, L. K., Ledbetter, J. A., Linsley, P. S., and Aruffo, A. 1994. Coengagement of CD2 with LFA-1 or VLA-4 by bispecific ligand fusion proteins primes T cells to respond more effectively to T cell receptor-dependent signals. J. Leukoc. Biol. 56:444–452.
Hibbs, M. L., Jakes, S., Stacker, S. A., Wallace, R. W., and Springer, T. A. 1991. The cytoplasmic domain of the lymphocyte function associated 1 B subunit: Sites required for binding to intracellular adhesion molecule 1 and the phorbol ester-stimulaled phosphorylation site. J. Exp. Med. 174:1227–1238.
Groux, H., Huet, S., Valentin, H., Pham, D., and Bernard, A. 1989. Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes. Nature 339:152–154.
Nojima, Y., Rothstein, D. M., Sugita, K., Schlossman, S. F., and Morimoto, C. 1992. Ligation of VLA-4 on T cells stimulates tyrosine phosphorylation of a 105-kD protein. J. Exp. Med. 175:1045–1053.
Groettrup, M., and von Boehmer, H. 1993. A role for a pre-T cell receptor in T-cell development. Immunol. Today 14:610–614.
Groettrup, M., Baron, A., Griffiths, G., Palacios, R., and von Boehmer, H. 1992. T cell receptor (TCR) beta chain homodimers on the surface of immature but not mature alpha, gamma, delta chain deficient T cell lines. EMBO J. 11:2735–2745.
Wilson, A., and MacDonald, H. R. 1995. Expression of genes encoding the pre-TCR and CD3 comoplex during thymus development. Int. Immunol. 7:1659–1664.
Kishi, H., Borgulya, P., Scott, B., Karjalainen, K., Traunecker, A., Kaufman, J., and von Boehmer, H. 1991. Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells. EMBO J. 10:93–100.
Mombaerts, P., Clarke, A. R., Rudnicki, M. A., Lacomini, J., Itohara, S., Lafaille, J. J., Wang, L., Ichikawa, Y., Jaenisch, R., Hooper M. L., and Tonegawa, S. 1992. Mutations in T-cell antigen receptor genes α and β block thymocytes development at different stages. Nature 360:225–231.
Shinkai, Y., Koyasu, S., Nakayama, K., Murphy, K. M., Loh, D. Y., Reinherz, E. L., and Alt, F. W. 1993. Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes. Science 259:822–825.
Snodgrass, H. R., Kisielow, P., Kiefer, M., Steinmetz, M., and von Boehmer, H. 1985. Ontogeny of the T-cell antigen receptor within the thymus. Nature 313:592–595.
Shortman, K., Vremec, D., and Egerton, M. 1991. The kinetics of T cell antigen receptor expression by subgroups of CD4+ 8+ thymocytes: Delineation of CD4+ 8+ 3(2+) thymocytes as post-selection inter-mediates leading to mature T cells. J. Exp. Med. 173:323–332.
Egerton, M., Scollay, R., and Shortman, K. 1990. Kinetics of mature T-cell development in the thymus. Proc. Natl. Acad. Sci. USA 87:2579–2582.
Huesmann, M., Scott, B., Kisielow, P., and von Boehmer, H. 1991. Kinetics and efficacy of positive selection in the thymus of normal and T cell receptor transgenic mice. Cell 66:533–540.
Haas, W., and Tonegawa, S. 1992. Development and selection of gamma delta T cells. Curr. Opin. Immunol. 4:147–155.
Allison, J. P. 1993. Gamma delta T-cell development. Curr. Opin. Immunol. 5:241–246.
Ferrick, D. A., Ohashi, P. S., Wallace, V., Schilham, M., and Mak, T. W. 1989. Thymic ontogeny and selection of alpha beta and gamma delta T cells. Immunol. Today 10:403–407.
Exley, M., Wileman, T., Mueller, B., and Terhorst, C. 1995. Evidence for multivalent structure of T-cell antigen receptor complex. Mol. Immunol. 32:829–839.
Motto, D. G., Ross, S. E., Wu, J., Hendricks-Taylor, L. R., and Koretzky, G. A. 1996. Implications of the grb2-associated phosphoprotein SLP-76 in T-cell receptor-mediated interleukin-2 production. J. Exp. Med. 183:1937–1943.
Ward, S. G., June, C. H., and Olive, D. 1996. PI-3-kinase—A pivotal pathway in T-cell activation. Immunol. Today 17:187–197.
Crooks, M. E. C., Littman, D. R., Carter, R. H., Fearon, D. T., Weiss, A., and Stein, P. H. 1995. CD28-mediated costimulation in the absence of phosphatidylinositol 3-kinase association and activation. Mol. Cell. Biol. 15:6820–6828.
Casolaro, V., Georas, S. N., Song, Z. M., Zubkoff, I. D., Abdulkadir, S. A., Thanos, D., and Ono, S. J. 1995. Inhibition of NF-AT-dependent transcription by NF-kappa-B—Implications for differential geneexpression in T-helper cell subsets. Proc. Natl. Acad. Sci. USA 92:11623–11627.
Jain, J., Valge Archer, V. E., Sinskey, A. J., and Rao, A. 1992. The AP-1 site at-150 bp, but not the NF-kappa B site, is likely to represent the major target of protein kinase C in the interleukin 2 promoter. J. Exp. Med. 175:853–862.
Fraser, J. D., Newton, M. E., and Weiss, A. 1992. CD28 and T cell antigen receptor signal transduction coordinately regulate interleukin 2 gene expression in response to superantigen stimulation. J. Exp. Med. 175:1131–1134.
Ghosh, S., and Baltimore, D. 1990. Activation in vitro of NF-kappaB by phosphorylation of its inhibitor IkappaB. Nature 344:678–682.
Civil, A., Bakker, A., Rensink, I., Doerre, S., Aarden, L. A., and Verweij, C. L. 1996. Nuclear appearance of a factor that binds the CD28 response element within the interleukin-2 enhancer correlates with interleukin-2 production. J. Biol. Chem. 271:8321–8327.
Sundstedt, A., Sigvardsson, M., Leanderson, T., Hedlund, G., and Dohlsten, M. 1996. In-vivo anergized CD4+ T-cells express perturbed AP-1 and NK-kappa-B transcription factors. Proc. Natl. Acad. Sci. USA 93:979–984.
Mouzaki, A., Serfling, E., and Zubler, R. H. 1995. Interleukin-2 promoter activity in Epstein-Barr virus-transformed B-lymphocytes is controlled by nuclear factor-chi-B. Eur. J. Immunol. 25:2177–2184.
Neumann, M., Grieshammer, T., Chuvpilo, S., Kneitz, B., Lohoff, M., Schimpl, A., Franza, B. R., Jr., and Serfling, E. 1995. RelA/p65 is a molecular target for the immunosuppressive action of protein kinase A. EMBO J. 14:1991–2004.
Segil, N., Boseman Roberts, S., and Heintz, N. 1991. Mitotic phosphorylation of the Oct-1 homeodomain and regulation of Oct-1 DNA binding activity. Science 254:1814–1816.
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(1998). T-Lymphocyte Genes. In: Handbook of Imune Response Genes. Springer, Boston, MA. https://doi.org/10.1007/978-0-585-31180-7_3
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