The γ-δ Heterodimer

A Second T-Cell Receptor?
  • Nicolette Caccia
  • Yoshihiro Takihara
  • Tak W. Mak


T cells play an important role in the mammalian immune system, participating in a number of cell-cell interactions. It is through these interactions, and the products that result from these interactions, that T cells aid in the regulation and differentiation of the immune response. T cells can be divided into those that mediate the cellular response (cytotoxic T lymphocytes) and those that regulate the humoral response (helper and suppressor T lymphocytes). Cytotoxic T lymphocytes (CTL) lyse abnormal host cells, including neoplastic cells and those infected by virus, while helper T lymphocytes (HTL) enhance the response of B cells and other T cells, and suppressor T cells down-regulate their response. T cells are closely related to B cells, which provide the fine tuning of the immune response by the production of immunoglobulins; antigen-specific molecules involved in a variety of immune reactions that lead to the elimination of antigen and the neutralization of antigen-bearing cells (Davies and Metzger, 1983; Honjo, 1983). Both B and T cells have diverse, clonally distributed repertoires, recognize antigen in a specific manner by means of cell surface receptors, and generate the genes that encode their receptors by the rearrangement of sequences that are noncontiguous in germ-line DNA, using the same enzyme system. However, there are a number of significant differences between the two cell types, including their products, specific functions, and modes of antigen recognition.


Chain Gene Gene Segment Mixed Lymphocyte Reaction Gamma Gene Cell Antigen Receptor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bank, I., DePinho, R.A., Brenner, M.B., Cassimeris, J., Alt, F.A., and Chess, L., 1986, A functional CD3 molecule associated with a novel heterodimer on the surface of immature human thymocytes, Nature 322:179–181.PubMedCrossRefGoogle Scholar
  2. Bluestone, J.A., Pardoll, D., Sharrow, S., and Fowlkes, B.J., 1987, Characterization of murine thymocytes with CD3-associated T-cell structures, Nature 326:82–84.PubMedCrossRefGoogle Scholar
  3. Born, W., Rathburn, G., Tucker, P., Marrack, P., and Kappler, J., 1986, Synchronized rearrangement of T cell γ and β chain genes during fetal thymocyte development, Science 234:479–482.PubMedCrossRefGoogle Scholar
  4. Born, W., Yague, J., Palmet, E., Kappler, J., and Marrack, P., 1985, Rearrangement of T-cell receptor β-chain genes during T cell development, Proc. Natl. Acad. Sci. USA 82:2925–2929.PubMedCrossRefGoogle Scholar
  5. Born, W, Miles, C., White, J., O’Brien, R., Freed, J.H., Marrack, P., Kappler, J., and Kubo, R.T., 1987, Peptide sequences of the T-cell receptor δ and γ chains are identical to predicted x and δ proteins, Nature 330:572–574.PubMedCrossRefGoogle Scholar
  6. Borst, J., Alexander, S., Elder, J., and Terhorst, C., 1983, The T3 complex on human T lymphocytes involves four structurally distinct glycoproteins, J. Biol. Chem. 258:5135–5143.PubMedGoogle Scholar
  7. Borst, J., van de Grund, R.J., van Osteen, J.W., Ang, S.L., Melief, C.J., Seidman, J.G., and Bolhuis, R.L.H., 1987, A T cell receptor gamma/CD3 complex on CD3+48 cloned cytolytic peripheral blood lymphocytes, Nature 325:683–688.PubMedCrossRefGoogle Scholar
  8. Boryhadi, M., Weiss, A., Tucker, P.W., Tigelaar, R.E., Allison, J.P., 1987, Delta is the Cx-gene product in the γ/δ antigen receptor in dendritic epidermal cells, Nature 330:574–576.CrossRefGoogle Scholar
  9. Brenner, M.B., MacLean, 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.PubMedCrossRefGoogle Scholar
  10. Brenner, B., McLean, J., Scheft, H., Riberdy, J., Ang, S., Siedman, J., Devlin, P., and Krangel, M.S., 1987, Two forms of the T cell receptor γ protein found on peripheral blood cytotoxic T lymphocytes, Nature 325:689–693.PubMedCrossRefGoogle Scholar
  11. Budd, R.C., Cerottini, J.C., and McDonald, H.R., 1986, Cultured Lyt2L3T4 T lymphocytes from normal thymus of mice express a broad spectrum of cytolytic activity, J. Imm. 137:3734–3741.Google Scholar
  12. Champagne, E., Takihara, Y., Sagman, U., Griesser, H., Tkachuk, D., Isuza, J., Mak, T.W., and Minden, M.D., 1987, The isolation of the human δ chain gene and its expression in normal T cells and T cell leukemias, (submitted).Google Scholar
  13. Chien, Y., Becker, D., Lindsten, T., Okamura, M., Cohen, D., and Davis, M., 1984a, A third type of murine T cell receptor gene, Nature 312:31–35.PubMedCrossRefGoogle Scholar
  14. Chien, Y.-H., Gascoigne, N.R.J., Kaveler, J., Lee, N.E., and David, M.M., 1984b, Somatic recombination in a murine T-cell receptor gene, Nature 309:322–326.PubMedCrossRefGoogle Scholar
  15. Chien, Y.-H., Iwashima, M., Kaplan, K.B., Elliot, J.F., and Davis, M.M., 1987a, A new T-cell receptor gene located in the alpha locus and expressed early in T cell differentiation, Nature 327:677–681.PubMedCrossRefGoogle Scholar
  16. Chien, Y.-H., Iwashima, M., Wittstein, D.A., Kaplan, K.B., Elliot, J.F., Born, W., and Davis, M.M., 1987b. T-cell receptor δ gene rearrangements in early thymocytes, Nature 330:722–727.PubMedCrossRefGoogle Scholar
  17. Davies, D.R., and Metzger, H., 1983, Structural basis of antibody function, Ann. Rev. Immunol. 1:63–86.CrossRefGoogle Scholar
  18. DelaHera, A., Toribo, M.L., Minguez, C., and Martinez, C., 1985, Interleukin-2 promotes growth and cytolytic activity in human T348 thymocytes, Proc. Natl. Acad. Sci. USA 82:6268–6271.CrossRefGoogle Scholar
  19. Dialynas, D.P., Murre, C., Quetermous, T., Boss, J., Leiden, J.M., Seidman, J.G., and Strominger, J.L., 1986, Cloning and sequence analysis of complementary DNA encoding an aberrantly rearranged human T cell γ chain, Proc. Natl. Acad. Sci. USA 83:2619–2613.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. Griesser, H., Champagne, E., Tkachok, D., Takihara, P., Lalande, M., Baillie, E., Minden, M.D., and Mak, T.W., 1987, Mapping of the human T cell receptor α-δ region: A locus with a new constant region gene and prone to multiple chromosomal translocations, (submitted).Google Scholar
  22. Haars, R., Kronenberg, M., Owen, F., Gallatin, M., Weissman, I., and Hood, L., 1986, Rearrangement and expression of T-cell antigen receptor and γ chain genes during thymic differentiation, J. Exp. Med. 164:1–24.PubMedCrossRefGoogle Scholar
  23. Haskins, K., Kappler, J., and Marrack, P., 1984, The major histocompatibility complex-restricted antigen receptor on T cells, Ann. Rev. Immunol. 2:51–66.CrossRefGoogle Scholar
  24. 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 γ genes, Cell 40:259–269.PubMedCrossRefGoogle Scholar
  25. Hedrick, S.M., Cohen, D.I., Nielsen, E.A., and Davis, 1984a, Isolation of cDNA clones encoding T cell specific membrane-associated proteins, Nature 308:149–152.PubMedCrossRefGoogle Scholar
  26. Hedrick, S.M., Nielsen, E.A., Kavaler, J., Cohen, D.I., Davis, M.M., 1984b, Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins, Nature 308:153–158.PubMedCrossRefGoogle Scholar
  27. Helig, J.S., and Tonegawa, S., 1986, Diversity of murine γ genes and expression in fetal and adult thymocytes, Nature 322:336–340.Google Scholar
  28. Helig, J.S., Glimcher, L.H., Kranz, D.M., Clayton, L.K., Greenstein, J.L., Saito, H., Maxam, A.M., Burakoff, S.J., Eisen, H.N., and Tonegawa, S., 1985, Expression of the T-cell specific γ gene is unnecessary in T cells recognizing class II MHC determinants, Nature 317:68–70.CrossRefGoogle Scholar
  29. Honjo, T., 1983, Immunoglobulin genes, Annu. Rev. Immunol. 1:499–528.PubMedCrossRefGoogle Scholar
  30. Iwamoto, I., Ohashi, P., Walker, C., Rupp, F., Yoho, H., Hengartner, H., and Mak, T.W., 1986, The murine γ chain genes in B10 mice: Sequence and expression of new constant and variable genes, J. Exp. Med. 163:1203–1212.PubMedCrossRefGoogle Scholar
  31. Jones, B., Mjolsness, S., Janeway, C., and Hayday, A.C., 1986, Transcripts of functionally rearranged gamma genes in primary T cells of immunocompetent mice, Nature 323:635–638.PubMedCrossRefGoogle Scholar
  32. Kappler, J., Kubo, R., Haskins, K., White, J., and Marrack, P., 1983, The mouse T-cell receptor: Comparison of MHC-restricted receptors on two T-cell hybridomas, Cell 34:727–737.PubMedCrossRefGoogle Scholar
  33. Kimura, N., Du, R.P., and Mak, T.W., Rearrangement and organization of T cell receptor gamma chain genes in human leukemic T cell lines, Eur. J. Immunol. (in press).Google Scholar
  34. Kishihara, K., Yoshikai, Y., Matsuzakai, G., Mak, T.W., and Nomoto, K., 1987, Functional α and β chain T cell receptor messages can be detected in old, but not young, athymic mice, Eur. J. Immunol. 17:477–482.PubMedCrossRefGoogle Scholar
  35. Krangel, M.S., Band, H., Hata, S., McLean, J., and Brenner, M.B., 1987, Structurally divergent human T cell receptor γ proteins encoded by distinct C γ genes, Science 237:64–67.PubMedCrossRefGoogle Scholar
  36. Kran, D.M., Saito, H., Disteche, C.M., Swisshelm, I., Pravtcheva, D., Ruddle, F., Eisen, H.N., and Tonegawa, J., 1985a, Chromosomal locations of the T-cell receptor α chain gene and the T cell α gene, Science 227:941–945.CrossRefGoogle Scholar
  37. Kranz, D.M., Saito, H., Heller, M., Takagaki, Y., Haas, W., Eisen, H., and Tonegawa, S., 1985b, Limited diversity of the rearranged T cell γ gene, Nature 313:752–755.PubMedCrossRefGoogle Scholar
  38. Lanier, L.L., Federspiel, N.A., Ruitenberg, J.J., Phillips, J.H., Allison, J.A., Littman, D., and Weiss, A., 1987, The T cell receptor complex expressed on normal peripheral blood CD4CD8 T lymphocytes: A CD3-associated disulphide-linked γ chain heterodimer, J. Exp. Med. 165:1067–1094.CrossRefGoogle Scholar
  39. Lanier, L.L., and Weiss, A., 1986, Presence of Ti(WT31) negative T lymphocytes in normal blood and thymus, Nature 324:268–270.PubMedCrossRefGoogle Scholar
  40. LeFranc, M.F., and Rabbitts, T., 1985, Two tandemly organized human genes encoding the T cell γ constant region sequences show multiple rearrangements in different T cell types, Nature 316:464–466.PubMedCrossRefGoogle Scholar
  41. LeFranc, M.F., Forster, A., and Rabbits, T.H., 1986a, Rearrangement of two distinct T cell γ chain genes variable region genes in human DNA, Nature 319:420–422.PubMedCrossRefGoogle Scholar
  42. LeFranc, M.F., Forster, A., and Rabbits, T.H., 1986b, Genetic polymorphism and exon changes of the constant regions of the human T cell rearranging gene γ, Proc. Natl. Acad. Sci. USA 83:9596–9600.PubMedCrossRefGoogle Scholar
  43. LeFranc, M.F., Forster, A., Baer, R., Stinson, M.A., and Rabbits, J., 1986c, Diversity and rearrangement of the human T cell rearranging γ genes: Nine germline variable genes belonging to two subgroups, Cell 45:237–247.PubMedCrossRefGoogle Scholar
  44. LeFranc, M.F., Forster, A., and Rabbitts, T., 1987, Organization of the human T cell rearranging gamma genes (TRG γ), in: The T cell receptor, UCLA symposia on Molecular and Cellular Biology, Volume 73 (J. Kappler and M. Davis, eds.), Alan R. Liss, New York, (in press).Google Scholar
  45. Lew, A.M., Pardoll, D.M., Maloy, W.L., Fowlkes, B.J., Kruisbeek, A., Cheng, S.F., Germain, R.H., Bluestone, J.A., Schwartz, R.H., and Coligan, J.E., 1986, Characterization of T cell receptor γ chain expression in a subset of murine thymocytes, Science 234:1401–1405.PubMedCrossRefGoogle Scholar
  46. Littman, D.G., Newton, M., Crommie, D., Ang, S.-L., Seidman, J.G., Gettner, S.N., and Weiss, A., 1987, Characterization of an expressed CD3-associated Ti γ-chain reveals C γ chain polymorphism, Nature 326:85–88.PubMedCrossRefGoogle Scholar
  47. Loh, E.Y., Lanier, I.L., Turck, C.W., Littman, D.R., Davis, M.M., Chien, Y.H., and Weiss, A., 1987, Identification and sequence of a fourth human T cell antigen receptor chain, Nature 330:569–572.PubMedCrossRefGoogle Scholar
  48. Maeda, K., Makamishi, M., Rogers, B., Haser, W.G., Shitara, K., Yoshida, H., Takagaki, Y., Augustin, A.A., and Tonegawa, S., 1987, Expression of the T cell receptor γ-chain gene product on the surface of peripheral T cells and T cell blasts generated by allogeneic mixed lymphocyte reaction, Proc. Natl. Acad. Sci. USA 84:6536–6540.PubMedCrossRefGoogle Scholar
  49. Matis, L.A., Cron, R., and Bluestone, J.A., 1987, Major histocompatibility complex-linked, specificity of γδ receptor-bearing T lymphocytes, Nature 330:262–264.PubMedCrossRefGoogle Scholar
  50. McIntyre, B.W., and Allison, J.P., 1983, The mouse T cell receptor: structural heterogeneity of molecules of normal T cells defined by xenoantiserum, Cell 34:739–746.PubMedCrossRefGoogle Scholar
  51. Miescher, G.C., Budd, R.C., Lees, R.K., and McDonald, H.R., 1967, Abnormal expression of T cell receptor genes in Lyt2 L3T4 lymphocytes of lpr mice: Comparison with normal immature thymocytes, J. Immunol. 138:1959.Google Scholar
  52. Meuer, S.C., Cooper, D.A., Hodgdon, J.C., Hussey, R.E., Fitzgerald, K.A., Schlossman, S., and Reinherz, E.L., 1983, Identification of the receptor for antigen and major histocompatibility complex on human inducer T lymphocytes, Science 222:1239–1242.PubMedCrossRefGoogle Scholar
  53. Moingeon, P., Ythier, A., Goubin, G., Faure, F., Nowill, A., Delmon, L., Rainand, M., Forestier, F., Daffos, F., Bohuon, C., and Hercend, T., 1986, A unique T-cell receptor complex expressed on human fetal lymphocytes displaying natural-killer-like activity, Nature 323:638–640.PubMedCrossRefGoogle Scholar
  54. Moingeon, P., Jitsukawa, S., Faure, F., Troalen, F., Triebel, F., Graziani, M., Forestier, F., Bellet, D., Bohoun, C., and Hercend, T., 1987, A γ chain complex forms a functional receptor on cloned human lymphocytes with natural killer-like activity, Nature 325:723–726.PubMedCrossRefGoogle Scholar
  55. Murre, C., Waldman, R.A., Morton, C.C., Bongiovanni, K.F., Waldman, T.A., Shows, T.B., and Seidman, J.G., 1985, Human γ chain genes are rearranged in leukemic T cells and map to the short arm of chromosome 7, Nature 316:549–552.PubMedCrossRefGoogle Scholar
  56. Nakashini, N., Maech, K., Ko-Ichi, I., Heller, M., and Tonegawa, S., 1987, γ protein is expressed on murine fetal thymocytes as a disulphide linked heterodimer, Nature 325:720–722.CrossRefGoogle Scholar
  57. Ohashi, P., 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 T3/T cell antigen receptor in human T cells by DNA transfer, Nature 316:602–606.CrossRefGoogle Scholar
  58. Pardoll, D.M., Fowlkes, B.J., Bluestone, J.A., Kruisbek, A., Maloy, W.L., Coligan, J.E., and Schwartz, R.H., 1987, Differential expression of two distinct T cell receptors during T cell development, Nature 326:79–81.PubMedCrossRefGoogle Scholar
  59. Raulet, D.H., Garman, R.D., Saito, H., and Tonegawa, S., 1985, Developmental regulation of T-cell receptor gene expression, Nature 314:103–107.PubMedCrossRefGoogle Scholar
  60. Reilly, A.E.B., Kranz, D.M., Tonegawa, S., and Eisen, H.N., 1986, A functional γ gene formed from known γ gene segments is not necessary for antigen-specific responses of murine cytotoxic T lymphocytes, Nature 321:878–881.PubMedCrossRefGoogle Scholar
  61. Rupp, F., Frech, G., Hengartner, H., Zinkernagel, R.M., and Joho, R., 1986, No functional γ-chain transcripts detected in an alloreactive cytotoxic T cell clone, Nature 321:876–878.PubMedCrossRefGoogle Scholar
  62. Saito, H., Kranz, D.M., Takagaki, Y., Hayday, A., Eisen, H., and Tonegawa, S., 1984a, A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes, Nature 312:36–40.PubMedCrossRefGoogle Scholar
  63. Saito, H., Kranz, D.M., Takagaki, Y., Hayday, A., Eisen, H., and Tonegawa, S., 1984b, Complete primary structure of a heterodimeric T cell receptor deduced from cDNA sequences, Nature 309:757–762.PubMedCrossRefGoogle Scholar
  64. Sim, G., Yague, J., Nelson, J., Marrack, P., Palmer, E., Augustin, A., and Kappler, J., 1984, Primary structure of human T cell receptor α chain, Nature 312:771–775.PubMedCrossRefGoogle Scholar
  65. Snodgrass, H.R., Dembic, Z., Steinmetz, M., and von Boehmer, H., 1985a, Expression of T-cell antigen receptor genes during fetal development in the thymus, Nature 313:232–233.CrossRefGoogle Scholar
  66. Snodgrass, H.R., Kisielow, P., Kiefer, M., Steinmetz, M., and von Boehmer, H., 1985b, Ontogeny of the T-cell antigen receptor within the thymus, Nature 313:592–595.PubMedCrossRefGoogle Scholar
  67. Takihara, Y., Champagne, E., Griesser, H., Kimura, M., Tkachuk, D., Reiman, J., Okada, A., Alt, F., Chess, L., Minden, M., and Mak, T.W., 1988a, The sequence and organization of the human T cell δ chain gene, Eur. J. Immunol (in press)Google Scholar
  68. Takihara, Y., Tkachuk, D., Michalopoulos, E., Champagne, E., Reimann, J., Minden, M., and Mak, T.W., 1988b, Sequence and organization of the diversity, joining and constant region genes of the human T-cell δ chain locus, (submitted).Google Scholar
  69. Toribo, M.L., Martinez, C., Marcos, M.A.R., Marquez, C., Calabraro, E., and DelaHera, A., 1986, A role for T3+468 transitional thymocytes in the differentiation of mature and functional T cells from human prothymocytes, Proc. Natl. Acad. Sci. USA 82:6985–6988.CrossRefGoogle Scholar
  70. Weiss, A., and Stobo, J.D., 1984, Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant T cell line, J. Exp. Med. 160:1284–1299.PubMedCrossRefGoogle Scholar
  71. Weiss, A., Newton, M., and Crommie, D., 1986a, Expression of T3 in association with a molecule distinct from the T cell antigen receptor heterodimer, Proc. Natl. Acad. Sci. USA 83:6998–7002.PubMedCrossRefGoogle Scholar
  72. Weiss, A., Imboden, J., Hardy, K., Manger, B., Terhorst, C., and Stobo, J., 1986b, The role of the CD3/antigen receptor complex in T cell activation, Annu. Rev. Immunol. 4:593–619.PubMedCrossRefGoogle Scholar
  73. Yanagi, Y., Chan, A., Chin, B., Minden, M., and Mak, T.W., 1985, Analysis of cDNA clones specific for human T cells and the α and β chain of the T cell receptor heterodimer from a human T cell line, Proc. Natl. Acad. Sci. USA 82:3430–3434.PubMedCrossRefGoogle Scholar
  74. Yanagi, Y., Yoshikai, Y., Leggett, K., Clark, S., Aleksander, I., and Mak, T.W., 1984, A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains, Nature 308:145–149.PubMedCrossRefGoogle Scholar
  75. Yoshikai, Y., Reis, M.D., and Mak, T.W., 1986a, Athymic mice express a high level of functional γ chain, but drastically reduced levels of α and β chain T cell receptor messages, Nature 324:482–485.PubMedCrossRefGoogle Scholar
  76. Yoshikai, Y., Toyonaga, B., Koga, Y., Kimura, N., Griesser, H., and Mak, T.W., 1987, Repertoire of the human T cell γ gene: high frequency of non-functional transcripts in thymus and mature T cells, Eur. J. Imm. 17:119–126.CrossRefGoogle Scholar
  77. Zauderer, M., Iwamoto, I., and Mak, T.W., 1986, Gamma gene expression in autoreactive helper T cells, J. Exp. Med. 163:1314–1318.PubMedCrossRefGoogle Scholar
  78. Zinkernagel, R.M., Doherty, P.C., 1974, Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system, Nature 248:701–702.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Nicolette Caccia
    • 1
    • 2
  • Yoshihiro Takihara
    • 1
    • 2
  • Tak W. Mak
    • 1
    • 2
  1. 1.The Ontario Cancer InstituteTorontoCanada
  2. 2.Department of Medical BiophysicsUniversity of TorontoTorontoCanada

Personalised recommendations