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Developmental Stage-Specific Responses to Ligation of CD3-Containing Complexes

  • Chapter
Molecular Biology of B-Cell and T-Cell Development

Part of the book series: Contemporary Immunology ((CONTIM))

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Abstract

The vast repertoire of T-cell receptor specificities is accomplished by somatic assembly of V, D, and J gene segments into genes encoding the T-cell receptor (TCR) -α and -β chains. Because chances are that this partially random process does not produce a useful TCR, several selection events are imposed on developing T-cells. These selection events are all controlled by signals transduced through TCR-CD3 complexes. The composition of the TCR-CD3 complex, the signals transduced by it, and the responses of the thymocytes differ at distinct stages of development. This chapter describes the molecular composition of the CD3-containing complexes, as well as the signals and maturation events that are inducible upon ligation with antibodies.

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References

  1. Wu, L., Scollay, R., Egerton, M., Pearse, M., Spangrude, G. J., and Shortman, K. ( 1991. CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus. Nature 349, 71–74.

    Article  PubMed  CAS  Google Scholar 

  2. Shortman, K. and Wu, L. (1996) Early T lymphocyte progenitors. Annu. Rev. Immunol. 14, 29–47.

    Article  PubMed  CAS  Google Scholar 

  3. Wilson, A. and MacDonald, H. R. (1995) Expression of genes encoding the pre-TCR and CD3 complex during thymus development. Int. Immunol. 7, 1659–1664.

    Article  PubMed  CAS  Google Scholar 

  4. Hozumi, K., Kondo, M., Nozaki, H., Kobori, A., Nishimura, T., Nishikawa, S., Sugamura, K., and Habu, S. (1994) Implication of the common gamma chain of the IL-7 receptor in intrathymic development of pro-T cells. Int. Immunol. 6, 1451–1454.

    Article  PubMed  CAS  Google Scholar 

  5. Peschon, J. J., Morrissey, P. J., Grabstein, K. H., Ramsdell, F. J., Maraskovsky, E., Gliniak, B. C., Park, L. S., Ziegler, S.F., Williams, D. E., Ware, C. B., et al. (1994) Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp. Med. 180, 1955–1960.

    Article  PubMed  CAS  Google Scholar 

  6. Rodewald, H. R., Kretzschmar, K., Swat, K., and Takeda, S. (1995) Intrathymically expressed c-kit ligand (stem cell factor) is a major factor driving expansion of very immature thymocytes in vivo. Immunity 3, 313–319.

    Article  PubMed  CAS  Google Scholar 

  7. von Freeden-Jeffry, U., Vieira, P., Lucian, L. A., McNeil, T., Burdach, S. E., and Murray, R. (1995) Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J. Exp. Med. 181, 1519–1526.

    Article  Google Scholar 

  8. Oosterwegel, M. A., Haks, M. C., Jeffry, U., Murray, R., and Kruisbeek, A. M. (1997) Induction of TCR gene rearrangements in uncommitted stem cells by a subset of IL-7 producing, MHC class-II-expressing thymic stromal cells. Immunity 6, 351–360.

    Article  PubMed  CAS  Google Scholar 

  9. Rodewald, H. R., Ogawa, M., Haller, C., Waskow, C., and DiSanto, J. P. (1997) Pro-thymocyte expansion by c-kit and the common cytokine receptor gamma chain is essential for repertoire formation. Immunity 6, 265–272.

    Article  PubMed  CAS  Google Scholar 

  10. Dudley, E. C., Girardi, M., Owen, M. J., and Hayday, A. C. (1995) Alpha beta and gamma delta T cells can share a late common precursor. Curr. Biol. 5, 659–669.

    Article  PubMed  CAS  Google Scholar 

  11. Kang, J., Baker, J., and Raulet, D. H. (1995) Evidence that productive rearrangements of TCR gamma genes influence the commitment of progenitor cells to differentiate into alpha beta or gamma delta T cells. Eur. J. Immunol. 25, 2706–2709.

    Article  PubMed  CAS  Google Scholar 

  12. Livak, F., Petrie, H. T., Crispe, I. N., and Schatz, D. G. (1995) In-frame TCR delta gene rearrangements play a critical role in the alpha beta/gamma delta T cell lineage decision. Immunity 2, 617–627.

    Article  PubMed  CAS  Google Scholar 

  13. Wilson, A., J. P. de Villartay and MacDonald, H. R. (1996) T cell receptor delta gene rearrangement and T early alpha (TEA) expression in immature alpha beta lineage thymocytes: implications for alpha beta/gamma delta lineage commitment. Immunity 4, 37–45.

    Article  PubMed  CAS  Google Scholar 

  14. Washburn, T., Schweighoffer, E., Gridley, T., Chang, D., Fowlkes, B. J., Cado, D., and Robey, E. (1997) Notch activity influences the aß versus yd T cell lineage decision. Cell 88, 833–843.

    Article  PubMed  CAS  Google Scholar 

  15. Godfrey, D. I., Kenney, J., Mombaerts, P., Tonegawa, S., and Zlotnik, A (1994) Onset of TCRbeta rearrangement and role of TCR-beta expression during CD3–CD4-CD8- thymocyte differentiation. J. Immunol. 152, 4783–4792.

    PubMed  CAS  Google Scholar 

  16. Hozumi, K., Kobori, A., Sato, T., Nozaki, H., Nishikawa, S., Nishimura, T., and Habu, S. (1994) Pro-T cells in fetal thymus express c-kit and RAG-2 but do not rearrange the gene encoding the T cell receptor beta chain. Eur. J. Immunol. 24, 1339–1344.

    Article  PubMed  CAS  Google Scholar 

  17. Wilson, A., Held, W., and MacDonald, H. R. (1994) Two waves of recombinase gene expression in developing thymocytes. J. Exp. Med. 179, 1355–1360.

    Article  PubMed  CAS  Google Scholar 

  18. Groettrup, M., U. K., Azogui, O., Palacios, R., Owen, M. J., Hayday, A. C., and von Boehmer, H. (1993) A novel disulfide-linked heterodimer on pre-T cells consists of the T cell receptor beta chain and a 33 kd glycoprotein. Cell 75, 283–294.

    CAS  Google Scholar 

  19. Saint-Ruf, C., Ungewiss, K., Groettrup, M., Bruno, L., Fehling, H. J., and von Boehmer, H. (1994) Analysis and expression of a cloned pre-T cell receptor gene. Science 266, 1208–1212.

    Article  PubMed  CAS  Google Scholar 

  20. Levin, S. D., Anderson, S. J., Forbush, K. A., and Perlmutter, R. M. (1993) A dominant-negative transgene defines a role for p561ck in thymopoiesis. EMBO J. 12, 1671–1680.

    PubMed  CAS  Google Scholar 

  21. Levelt, C. N., Wang, B., Ehrfeld, A., Terhorst, C., and Eichmann, K. (1995) Regulation of T cell receptor (TCR)-beta locus allelic exclusion and initiation of TCR-alpha locus rearrangement in immature thymocytes by signaling through the CD3 complex. Eur. J. Immunol. 25, 1257–1261.

    Article  PubMed  CAS  Google Scholar 

  22. Kisielow, P., Teh, H. S., Bluthmann, H., and von Boehmer, H. (1988) Positive selection of antigen-specific T cells in thymus by restricting MHC molecules. Nature 335, 730–733.

    Article  PubMed  CAS  Google Scholar 

  23. Gold, D. P., Clevers, H., Alarcon, B., Dunlap, S., Novotny, J., Williams, A. F., and Terhorst, C. (1987) Evolutionary relationship between the T3 chains of the T-cell receptor complex and the immunoglobulin supergene family. Proc. Natl. Acad. Sci. USA 84, 7649–7653.

    Google Scholar 

  24. Mallabiabarrena, A., Fresno, M., and Alarcon, B. (1992) An endoplasmic reticulum retention signal in the CD3 epsilon chain of the T-cell receptor. Nature 357, 593–596.

    Article  PubMed  CAS  Google Scholar 

  25. Weissman, A. M., Hou, D., Orloff, D. G., Modi, W. S., Seuanez, H., O’Brien, S. J., and Klausner, R. D. (1988) Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex. Proc. Natl. Acad. Sci. USA 85, 9709–9713.

    Article  PubMed  CAS  Google Scholar 

  26. Kuster, H., Thompson, H., and Kinet, J. P. (1990) Characterization and expression of the gene for the human Fc receptor gamma subunit. Definition of a new gene family. J. Biol. Chem. 265, 6448–6452.

    PubMed  CAS  Google Scholar 

  27. Kearse, K. P., Roberts, J. L., and Singer, A. (1995) TCR alpha-CD3 delta epsilon association is the initial step in aß dimer formation in murine T cells and is limiting in immature CD4+ CD8+ thymocytes. Immunity 2, 391–399.

    Article  PubMed  CAS  Google Scholar 

  28. Punt, J. A., Roberts, J. L., Kearse, K. P. and Singer, A. (1994) Stoichiometry of the T cell antigen receptor (TCR) complex: each TCR/CD3 complex contains one TCR alpha, one TCR beta, and two CD3 epsilon chains. J. Exp. Med. 180, 587–593.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. 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.

    Article  PubMed  CAS  Google Scholar 

  31. Liu, C. P., Ueda, R., She, J., Sancho, J., Wang, B., Weddell, G., Loring, J., Kurahara, C., Dudley, E. C., Hayday, A., et al. (1993) Abnormal T cell development in CD3-zeta-/- mutant mice and identification of a novel T cell population in the intestine. EMBO J. 12, 4863–4875.

    PubMed  CAS  Google Scholar 

  32. Love, P. E., Shores, E. W., Johnson, M. D., Tremblay, M. L., Lee, E. J., Grinberg, A., Huang, S. P., Singer, A., and Westphal, H. (1993) T cell development in mice that lack the zeta chain of the T cell antigen receptor complex. Science 261, 918–921.

    Article  PubMed  CAS  Google Scholar 

  33. Malissen, M., Gillet, A., Rocha, B., Trucy, J., Vivier, E., Boyer, C., Kontgen, F., Brun, N., Mazza, G., Spanopoulou, E., et al. (1993) T cell development in mice lacking the CD3-zeta/eta gene. EMBO J. 12, 4347–4355.

    PubMed  CAS  Google Scholar 

  34. Ohno, H., Goto, S., Taki, S., Shirasawa, T., Nakano, H., Miyatake, S., Aoe, T., Ishida, Y., Maeda, H., Shirai, T. et al. (1994) Targeted disruption of the CD3 eta locus causes high lethality in mice: modulation of Oct-1 transcription on the opposite strand. EMBO J. 13, 1157–1165.

    Google Scholar 

  35. van Oers, N. S., von Boehmer, H., and Weiss, A. (1995) The pre-T cell receptor (TCR) complex is functionally coupled to the TCR-zeta subunit. J. Exp. Med. 182, 1585–1590.

    Article  PubMed  Google Scholar 

  36. Levelt, C. N., Ehrfeld, A., and Eichmann, K. (1993) Regulation of thymocyte development through CD3. I. Timepoint of ligation of CD3 epsilon determines clonal deletion or induction of developmental program. J. Exp. Med. 177, 707–716.

    Article  PubMed  CAS  Google Scholar 

  37. Levelt, C. N., Mombaerts, P., Iglesias, A., Tonegawa, S., and Eichmann, K. (1993) Restoration of early thymocyte differentiation in T-cell receptor beta-chain-deficient mutant mice by transmembrane signaling through CD3 epsilon. Proc. Natl. Acad. Sci. USA 90,11, 401–11, 405.

    Google Scholar 

  38. Jacobs, H., Vandeputte, D., Tolkamp, L., de, V. E., Borst, J., and Berns, A. (1994) CD3 components at the surface of pro-T cells can mediate pre-T cell development in vivo. Eur. J. Immunol. 24, 934–939.

    Article  PubMed  CAS  Google Scholar 

  39. Shinkai, Y. and Alt, F. W. (1994) CD3 epsilon-mediated signals rescue the development of CD4+CD8+ thymocytes in RAG-2-/- mice in the absence of TCR beta chain expression. Int. Immunol. 6, 995–1001.

    Article  PubMed  CAS  Google Scholar 

  40. Wiest, D. L., Kearse, K. P., Shores, E. W. and Singer, A. (1994) Developmentally regulated expression of CD3 components independent of clonotypic T cell antigen receptor complexes on immature thymocytes. J. Exp. Med. 180, 1375–1382.

    Article  PubMed  CAS  Google Scholar 

  41. Wiest, D. L., Bhandoola, A., Punt, J., Kreibich, G., McKean, D., and Singer, A. (1997) Incomplete endoplasmic reticulum (ER) retention in immature thymocytes as revealed by surface expression of “ER-resident” molecular chaperones. Proc. Natl. Acad. Sci. USA 94, 1884–1889.

    Article  PubMed  CAS  Google Scholar 

  42. Malissen, M., Gillet, A., Ardouin, L., Bouvier, G., Trucy, J., Ferrier, P., Vivier, E., and Malissen, B. (1995) Altered T cell development in mice with a targeted mutation of the CD3- epsilon gene. EMBO J. 14, 4641–4653.

    PubMed  CAS  Google Scholar 

  43. Bosma, M. J. and Carroll, A. M. (1991) The Scid mouse mutant: definition, characterization and potential uses. Annu. Rev. Immunol. 9, 323–335.

    Article  PubMed  CAS  Google Scholar 

  44. Mombaerts, P., Clarke, A. R., Rudnicki, M. A., Iacomini, J., Itohara, S., Lafaille, J. J., Wang, L., Ichikawa, Y., Jaenisch, R., Hooper, M. L., et al. (1992) Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. Nature 360, 225–231.

    Article  PubMed  CAS  Google Scholar 

  45. 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.

    Google Scholar 

  46. Shinkai, Y., G. Rathbun, K. P. Lam, E. M. Oltz, V. Stewart, M. Mendelsohn, J. Charron, M. Datta, F. Young, A. M. Stall et al. ( 1992. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68, 855–867.

    Article  PubMed  CAS  Google Scholar 

  47. 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.

    Article  PubMed  CAS  Google Scholar 

  48. Fehling, H. J., Krotkova, A., Saint-Ruf, C., and von Boehmer, H. (1995) Crucial role of the preT-cell receptor alpha gene in development of alpha beta but not gamma delta T cells. Nature 375, 795–798.

    Article  PubMed  CAS  Google Scholar 

  49. Xu, Y., Davidson, L., Alt, F. W., and Baltimore, D. (1996) Function of the pre-T-cell receptor alpha chain in T-cell development and allelic exclusion at the T-cell receptor beta locus. Proc Natl. Acad. Sci. USA 93, 2169–2173.

    Article  PubMed  CAS  Google Scholar 

  50. Prosser, H. M. and Tonegawa, S. (1995) T cell receptor V(D)J recombination: mechanisms and developmental regulation, in T Cell Receptors ( Bell, J. I., Owen, M. J., and Simpson, E., eds.) Oxford, Oxford University Press, pp. 326–351.

    Google Scholar 

  51. Levelt, C. N., Carsetti, R., and Eichmann, K. (1993) Regulation of thymocyte development through CD3. II. Expression of T cell receptor beta CD3 epsilon and maturation to the CD4+8+ stage are highly correlated in individual thymocytes. J. Exp. Med. 178, 1867–1875.

    Article  PubMed  CAS  Google Scholar 

  52. Mallick, C. A., Dudley, E. C., Viney, J. L., Owen, M. J., and Hayday, A. C. (1993) Rearrangement and diversity of T cell receptor beta chain genes in thymocytes: a critical role for the beta chain in development. Cell 73, 513–519.

    Article  PubMed  CAS  Google Scholar 

  53. Borgulya, P., Kishi, H., Uematsu, Y., and von Boehmer, H. (1992) Exclusion and inclusion of alpha and beta T cell receptor alleles. Cell 69, 529–536.

    Article  PubMed  CAS  Google Scholar 

  54. Molina, T. J., Kishihara, K., Siderovski, D. P., van Ewijk, W., Narendran, A., Timms, E., Wakeham, A., Paige, C. J., Hartmann, K. U., Veillette, A., et al. (1992) Profound block in thymocyte development in mice lacking p56“. Nature 357, 161–164.

    Article  PubMed  CAS  Google Scholar 

  55. Anderson, S. J., Abraham, K. M., Nakayama, T., Singer, A., and Perlmutter, R. M. (1992) Inhibition of T-cell receptor beta-chain gene rearrangement by overexpression of the non-receptor protein tyrosine kinase p561ck. EMBO J. B 4877–4886.

    Google Scholar 

  56. Mombaerts, P., Anderson, S. J., Perlmutter, R. M., Mak, T. W., and Tonegawa, S. (1994) An activated lck transgene promotes thymocyte development in RAG-1 mutant mice. Immunity 1, 261–267.

    Article  PubMed  CAS  Google Scholar 

  57. Anderson, S. J., Levin, S. D., and Perlmutter, R. M. (1993) Protein tyrosine kinase p561ck controls allelic exclusion of T-cell receptor beta-chain genes. Nature 365, 552–554.

    Article  PubMed  CAS  Google Scholar 

  58. Wallace, V. A., Kawai, K., Levelt, C. N., Kishihara, K., Molina, T., Timms, E., Pircher, H., Penninger, J., Ohashi, P. S., Eichmann, K., et al. (1995) T lymphocyte development in p56lck deficient mice: allelic exclusion of the TCR beta locus is incomplete but thymocyte development is not restored by TCR beta or TCR alpha beta transgenes. Eur. J. Immunol. 25, 1312–1318.

    Article  PubMed  CAS  Google Scholar 

  59. Groves, T., Smiley, P., Cooke, M. P., Forbush, K., Perlmutter, R. M., and Guidos, C. J. (1996) Fyn can partially substitute for Lck in T lymphocyte development. Immunity 5, 417–428.

    Article  PubMed  CAS  Google Scholar 

  60. van Oers, N. S., Lowin, K. B., Finlay, D., Connolly, K., and Weiss, A. (1996) alpha beta T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases. Immunity 5, 429–436.

    Google Scholar 

  61. Levelt, C. N., Mombaerts, P., Wang, B., Kohler, H., Tonegawa, S., Eichmann, K., and Terhorst, C. (1995) Regulation of thymocyte development through CD3, functional dissociation between p561ck and CD3 sigma in early thymic selection. Immunity 3, 215–222.

    Article  PubMed  CAS  Google Scholar 

  62. Wang, C. R., Hashimoto, K., Kubo, S., Yokochi, T., Kubo, M., Suzuki, M., Suzuki, K., Tada, T., and Nakayama, T. (1995) T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thymic selection: requirement of calcineurin activation for thymic positive selection but not negative selection. J. Exp. Med. 181, 927–941.

    Article  PubMed  CAS  Google Scholar 

  63. Shinkai, Y., Ma, A., Cheng, H. L., and Alt, F. W. (1995) CD3 epsilon and CD3 zeta cytoplasmic domains can independently generate signals for T cell development and function. Immunity 2, 401–411.

    Article  PubMed  CAS  Google Scholar 

  64. Dave, V. P., Cao, Z., Browne, C., Alarcon, B., Fernandez-Miguel, G., Lafaille, J., de la Hera, A., Tonegawa, S., and Kappes, D. J. (1997) CD3delta deficiency arrests development of the alpha beta but not the gamma delta T cell lineage. EMBO J. 16, 1360–1370.

    Article  PubMed  CAS  Google Scholar 

  65. Negishi, I. Motoyama, N., Nakayama, K., Nakayama, K., Senju, S., Hatakeyama, S., Zhang, Q., Chan, A. C., and Loh, D. Y. (1995) Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature 376 435–438.

    Google Scholar 

  66. Alberola-Ila, J., Forbush, K. A., Seger, R., Krebs, E. G., and Perlmutter, R. M. (1995) Selective requirement for MAP kinase activation in thymocyte differentiation. Nature 373, 620–623.

    Article  PubMed  CAS  Google Scholar 

  67. Alberola-Ila, J., K. A. Hogquist, K. A. Swan, M. J. Bevan and R. M. Perlmutter. (1996) Positive and negative selection invoke distinct signaling pathways. J. Exp. Med. 184, 9–18.

    Article  PubMed  CAS  Google Scholar 

  68. Swan, K. A., Alberola-Ila, J., Gross, J. A., Appleby, M. W., Forbush, K. A., Thomas, J. F. and Perlmutter, R. M. (1995) Involvement of p2lras distinguishes positive and negative selection in thymocytes. EMBO J. 14, 276–285.

    PubMed  CAS  Google Scholar 

  69. Crompton, T., Gilmour, K. C., and Owen, M. J. (1996) The MAP kinase pathway controls differentiation from double-negative to double-positive thymocyte. Cell 86, 243–251.

    Article  PubMed  CAS  Google Scholar 

  70. Swat, W., Shinkai, Y., Cheng, H. L., Davidson, L. and Alt, F. W. (1996) Activated Ras signals differentiation and expansion of CD4+8+ thymocytes. Proc. Natl. Acad. Sci. USA 93, 4683–4687.

    Article  PubMed  CAS  Google Scholar 

  71. Benoist, B. and Mathis, D. (1997) Positive selection ofT cells: fastidious or promiscuous? Curr. Opin. Immunol. 9, 245–249.

    Article  PubMed  CAS  Google Scholar 

  72. Marrack, P. and Kappler, J. (1997) Positive selection of thymocytes bearing aß T cell receptors. Curr. Opin. Immunol. 9 250–255.

    Google Scholar 

  73. Ashton-Rickardt, P., Bandeira, A., Delaney, J. R., van Kaer, L., Pircher, H. P., Zinkernagel, R. M. and Tonegawa, S. (1994) Evidence for a differential avidity model of T cell selection in the thymus. Cell 76, 651–663.

    Article  PubMed  CAS  Google Scholar 

  74. Hogquist, K. A., Jameson, S. C., Heath, W. R., Howard, J. L., Bevan, M. J. and Carbone, F. R. (1994) T cell receptor antagonist peptides induce positive selection. Cell 76, 17–27.

    Article  PubMed  CAS  Google Scholar 

  75. Petrie, H. T., Livak, F., Schatz, D. G., Strasser, A., Crispe, I. N. and Shortman, K. (1993) Multiple rearrangements in T cell receptor alpha chain genes maximize the production of useful thymocytes. J. Exp. Med. 178, 615–622.

    Article  PubMed  CAS  Google Scholar 

  76. Robey, E. A., Fowlkes, B. J., Gordon, J. W., Kioussis, D., von, B. H., Ramsdell, F., and Axel, R. (1991) Thymic selection in CD8 transgenic mice supports an instructive model for commitment to a CD4 or CD8 lineage. Cell 64, 99–107.

    Google Scholar 

  77. Itano, A., Cado, D., Chan, F. K., and Robey, E. (1994) A role for the cytoplasmic tail of the beta chain of CD8 in thymic selection. Immunity 1, 287–290.

    Article  PubMed  CAS  Google Scholar 

  78. Itano, A., Salmon, P., Kioussis, D., Tolaini, M., Corbella, P. and Robey, E. (1996) The cytoplasmic domain of CD4 promotes the development of CD4 lineage T cells. J. Exp. Med. 183, 731–741.

    Article  PubMed  CAS  Google Scholar 

  79. Chan, S. H., Cosgrove, D., Waltzinger, C., Benoist, C., and Mathis, D. (1993) Another view of the selective model of thymocyte selection. Cell 73, 225–236.

    Article  PubMed  CAS  Google Scholar 

  80. Crump, A. L., Grusby, M. J., Glimcher, L. H., and Cantor, H. (1993) Thymocyte development in major histocompatibility complex-deficient mice: evidence for stochastic commitment to the CD4 and CD8 lineages. Proc. Natl. Acad. Sci. USA 90, 10739–10743.

    Article  PubMed  CAS  Google Scholar 

  81. Davis, C. B., Killeen, N., Crooks, M. E., Raulet, D., and Littman, D. R. (1993) Evidence for a stochastic mechanism in the differentiation ofmature subsets of T lymphocytes. Ce1173, 237–247.

    Google Scholar 

  82. Punt, J. A., Suzuki, H., Granger, L. G., Sharrow, S. O., and Singer, A. (1996) Lineage commitment in the thymus: only the most differentiated (TCRh’bcl-2h9 subset of CD4+CD8+ thymocytes has selectively terminated CD4 or CD8 synthesis. J. Exp. Med. 184, 2091–2099.

    Google Scholar 

  83. Suzuki, H., Punt, J. A., Granger, L. G., and Singer, A. (1995) Asymmetric signaling requirements for thymocyte commitment to the CD4+ versus CD8+ T cell lineages: a new perspective on thymic commitment and selection. Immunity 2, 413–425.

    Article  PubMed  CAS  Google Scholar 

  84. Robey, E., Chang, D., Itano, A., Cado, D., Alexander, H., Lans, D., Weinmaster, G., and Salmon, P. (1996) An activated form of Notch influences the choice between CD4 and CD8 T cell lineages. Cell 87, 483–492.

    Article  PubMed  CAS  Google Scholar 

  85. Alam, S. M., Travers, P. J., Wung, J. L., Nasholds, W., Redpath, S., Jameson, S. C., and Gascoigne, N. R. (1996) T-cell-receptor affinity and thymocyte positive selection. Nature 381, 616–620.

    Article  PubMed  CAS  Google Scholar 

  86. Hogquist, K. A., Jameson, S. C., and Bevan, M. J. (1995) Strong agonist ligands for the T cell receptor do not mediate positive selection of functional CD8+ T cells. Immunity 3, 79–86.

    Article  PubMed  CAS  Google Scholar 

  87. Fung, L. W., Surh, C. D., Liljedahl, M., Pang, J., Leturcq, D., Peterson, P. A., Webb, S. R., and Karlsson, L. (1996) Antigen presentation and T cell development in H2-M-deficient mice. Science 271, 1278–1281.

    Article  Google Scholar 

  88. Ignatowicz, L., Kappler, J., and Marrack, P. (1996) The repertoire of T cells shaped by a single MHC/peptide ligand. Cell 84, 521–529.

    Article  PubMed  CAS  Google Scholar 

  89. Martin, W. D., Hicks, G. G., Mendiratta, S. K., Leva, H. I., Ruley, H. E., and Van, K. L. (1996) H2-M mutant mice are defective in the peptide loading of class II molecules, antigen presentation, and T cell repertoire selection. Cell 84, 543–550.

    Google Scholar 

  90. Miyazaki, T., Wolf, P., Tourne, S., Waltzinger, C., Dierich, A., Barois, N., Ploegh, H., Benoist, C., and Mathis, D. (1996) Mice lacking H2-M complexes, enigmatic elements of the MHC class II peptide-loading pathway. Cell 84, 531–541.

    Article  PubMed  CAS  Google Scholar 

  91. Smith, C. A., Williams, G. T., Kingston, R., Jenkinson, E. J., and Owen, J. J. (1989) Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature 337, 181–184.

    Article  PubMed  CAS  Google Scholar 

  92. McConkey, D. J., Fosdick, L., D’Adamio, L., Jondal, M., and Orrenius, S. (1994) Co-receptor (CD4/CD8) engagement enhances CD3-induced apoptosis in thymocytes. Implications for negative selection. J. Immunol. 153, 2436–2443.

    PubMed  CAS  Google Scholar 

  93. Punt, J. A., Osborne, B. A., Takahama, Y., Sharrow, S. O., and Singer, A. (1994) Negative selection of CD4+CD8+ thymocytes by T cell receptor-induced apoptosis requires a costimulatory signal that can be provided by CD28. J. Exp. Med. 179, 709–713.

    Article  PubMed  CAS  Google Scholar 

  94. Zhao,Y. and lwata,M. (1995) Cross-linking oftheTCR-CD3 complex with CD4, CD8 orLFA-1 induces an anti-apoptotic signal in thymocytes: the signal is canceled by FK506. Int. Immunol. 7, 1387–1396.

    Article  Google Scholar 

  95. Noda, S., Kosugi, A., Saitoh, S., Narumiya, S., and Hamaoka, T. (1996) Protection from antiTCR/CD3-induced apoptosis in immature thymocytes by a signal through thymic shared antigen-1/stem cell antigen-2. J. Exp. Med. 183, 2355–2360.

    Google Scholar 

  96. 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, 609–612.

    Google Scholar 

  97. Shier, P., Otulakowski, G., Ngo, K., Panakos, J., Chourmouzis, E., Christjansen, L., Lau, C. Y., and Fung, L. W. (1996) Impaired immune responses toward alloantigens and tumor cells but normal thymic selection in mice deficient in the beta2 integrin leukocyte function-associated antigen-1. J. Immunol. 157, 5375–5386.

    PubMed  CAS  Google Scholar 

  98. Amakawa, R., Hakem, A., Kundig, T. M., Matsuyama, T., Simard, J. J., Timms, E., Wakeham, A., Mittruecker, H. W., Griesser, H. Takimoto, H., et al. (1996) Impaired negative selection of T cells in Hodgkin’s disease antigen CD30-deficient mice. Cell 84 551–562.

    Google Scholar 

  99. Foy, T. M., Page, D. M., Waldschmidt, T. J., Schoneveld, A., Laman, J. D., Masters, S. R., Tygrett, L., Ledbetter, J. A., Aruffo, A., Claassen, E., et al. (1995) An essential role for gp39, the ligand for CD40, in thymic selection. J. Exp. Med. 182, 1377–1388.

    Google Scholar 

  100. Muller, K. P. and Kyewski, B. A. (1993) T cell receptor targeting to thymic cortical epithelial cells in vivo induces survival, activation and differentiation of immature thymocytes. Eur. J. Immunol. 23, 1661–1670.

    Article  PubMed  CAS  Google Scholar 

  101. Takahama, Y., Suzuki, H., Katz, K. S., Grusby, M. J., and Singer, A. (1994) Positive selection of CD4+ T cells by TCR ligation without aggregation even in the absence of MHC. Nature 371, 67–70.

    Article  PubMed  CAS  Google Scholar 

  102. Cibotti, R., Punt, J. A., Dash, K. S., Sharrow, S. O. and Singer, A. (1997) Surface molecules that drive T cell development in vitro in the absence of thymic epithelium and in the absence of lineage—specific signals. Immunity 6, 245–255.

    Article  PubMed  CAS  Google Scholar 

  103. McConkey, D. J., Hartzell, P., Orrenius, S., and Jondal, M. (1989) Calcium-dependent killing of immature thymocytes by stimulation via the CD3/T cell receptor complex. J. Immunol. 143, 1801–1806.

    Google Scholar 

  104. Nakayama, T., Ueda, Y., Yamada, H. Shores, E. W., Singer, A., and June, C. H. (1992. In vivo calcium elevations in thymocytes with T cell receptors that are specific for self ligands. Science 257 96–99.

    Google Scholar 

  105. Vasquez, N. J., Kane, L. P., and Hedrick, S. M. (1994) Intracellular signals that mediate thymic negative selection. Immunity 1, 45–56.

    Article  PubMed  CAS  Google Scholar 

  106. Anderson, K. L., Anderson, G., Michell, R. H., Jenkinson, E. J., and Owen, J. J. (1996) Intracellular signaling pathways involved in the induction of apoptosis in immature thymic T lymphocytes. J. Immunol. 156, 4083–4091.

    Google Scholar 

  107. Conroy, L. A., Jenkinson, E. J., Owen, J. J., and Michell, R. H. (1995) Phosphatidylinositol 4,5bisphosphate hydrolysis accompanies T cell receptor-induced apoptosis of murine thymocytes within the thymus. Eur. J. Immunol. 25, 1828–1835.

    Article  PubMed  CAS  Google Scholar 

  108. O’Shea, C. C., Crompton, T., Rosewell, I. R., Hayday, A. C., and Owen, M. J. (1996) Raf regulates positive selection. Eur. J. Immunol. 26, 2350–2355.

    Article  PubMed  Google Scholar 

  109. Ohoka, Y., Kuwata, T., Tozawa, Y., Zhao, Y., Mukai, M., Motegi, Y., Suzuki, R., Yokoyama, M., and Iwata, M. (1996) In vitro differentiation and commitment of CD4+ CD8+ thymocytes to the CD4 lineage, without TCR engagement. Int. Immunol. 8, 297–306.

    Article  PubMed  CAS  Google Scholar 

  110. Takahama, Y. and Nakauchi, H. (1996) Phorbol ester and calcium ionophore can replace TCR signals that induce positive selection of CD4 T cells. J. Immunol. 157, 1508–1513.

    PubMed  CAS  Google Scholar 

  111. Izquirdo-Pastor, M., Reif, K., and Cantrell, D. (1995) The regulation and function of p21’as during T-cell activation and growth. Immunol. Today 16, 159–164.

    Article  Google Scholar 

  112. Hall, C. G., Sancho, J., and Terhorst, C. (1993) Reconstitution of T cell receptor zeta-mediated calcium mobilization in nonlymphoid cells. Science 261, 915–918.

    Article  PubMed  CAS  Google Scholar 

  113. Appleby, M. W., Gross, J. A., Cooke, M. P., Levin, S. D., Qian, X., and Perlmutter, R. M. (1992) Defective T cell receptor signaling in mice lacking the thymic isoform ofp59fY“. Cell 70, 751–763.

    Article  PubMed  CAS  Google Scholar 

  114. Stein, P. L., Lee, H. M., Rich, S., and Soriano, P. (1992) pp59fY“ mutant mice display differential signaling in thymocytes and peripheral T cells. Cell 70, 741–750.

    Google Scholar 

  115. Wiest, D. L., Ashe, J. M., Abe, R., Bolen, J. B., and Singer, A. (1996) TCR activation of ZAP70 is impaired in CD4+CD8+ thymocytes as a consequence of intrathymic interactions that diminish available p56lck. Immunity 4, 495–504.

    Article  PubMed  CAS  Google Scholar 

  116. Lerner, A., Clayton, L. K., Mizoguchi, E., Ghendler, Y., van Ewijk, W., Koyasu, S., Bhan, A. K., and Reinherz, E. L. (1996) Cross-linking of T-cell receptors on double-positive thymocytes induces a cytokine-mediated stromal activation process linked to cell death. EMBO J. 15, 5876–5887.

    PubMed  CAS  Google Scholar 

  117. Falk, I., Potocnik, A. J., Barthlott, T., Levelt, C. N., and Eichmann, K. (1996) Immature T cells in peripheral lymphoid organs of recombinase-activating gene-1/-2-deficient mice. Thymus dependence and responsiveness to anti-CD3 epsilon antibody. J. Immunol. 156, 1362–1368.

    PubMed  CAS  Google Scholar 

  118. Clegg, C. H., Rulffes, J. T., Wallace, P. M., and Haugen, H. S. (1996) Regulation of an extrathymic T-cell development pathway by oncostatin M. Nature 384, 261–263.

    Article  PubMed  CAS  Google Scholar 

  119. She, J., Simpson, S. J., Gupta, A., Hollaender, G., Levelt, C., Liu, C. P., Allen, D., van Houten, N., Wang, B., and Terhorst, C. (1997) CD16-Expressing CD8a/a+ T lymphocytes in the intestinal epithelium: Possible precursors of FcyR-CD8a/a+ T cells. J. Immunol. 158, 4678–4687.

    PubMed  CAS  Google Scholar 

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  1. Christiaan N. Levelt
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  1. University of Pennsylvania, Philadelphia, PA, USA

    John G. Monroe

  2. California Institute of Technology, Pasadena, CA, USA

    Ellen V. Rothenberg

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Levelt, C.N. (1998). Developmental Stage-Specific Responses to Ligation of CD3-Containing Complexes. In: Monroe, J.G., Rothenberg, E.V. (eds) Molecular Biology of B-Cell and T-Cell Development. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2778-4_23

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  • DOI: https://doi.org/10.1007/978-1-4757-2778-4_23

  • Publisher Name: Humana Press, Totowa, NJ

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