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The Murine T-Cell Antigen: Ia Receptor: Functional and Structural Analysis with a Monoclonal Antireceptor Antibody

  • Jonathan Kaye

Abstract

Antigen specificity is intrinsic to the T-cell as well as the B-cell compartment of an immune response. However, the term T cell applies to a heterogeneous population of lymphocytes. T cells were originally divided into subsets based on apparent function, subsequently classified by surface phenotype, and more recently classified by their antigen recognition properties. As a population, T cells are capable of recognizing a large number of diverse antigens. Like B-cell antigen recognition, mediated by membrane immunoglobulin, T-cell antigen recognition is a clonally distributed property such that any given T cell and its progeny are, allowing for an expected degree of cross-reactivity, monospecific. Unlike B cells, however, helper T lymphocytes, which induce B-cell growth and antibody secretion, and cytolytic T cells, which are capable of destroying virally infected cells, only recognize foreign antigen in conjunction with self major histocompatibility complex (MHC) glycoproteins on the surface of another cell. In immunologic slang, the dual specificity of these T-cell subsets for foreign antigen and self MHC molecules has been termed “MHC restriction,” since the ability of the T cell to recognize foreign antigen in this case is restricted by MHC molecules. In general, helper T cells recognize antigen in conjunction with class II MHC molecules (Ia antigens), and cytolytic T cells recognize foreign antigen in conjunction with class I MHC molecules.

Keywords

Major Histocompatibility Complex Antigen Receptor Major Histocompatibility Complex Molecule Accessory Cell Major Histocompatibility Complex Restriction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Allison, J. P., McIntyre, B. W., and Bloch, D., 1982, Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody, J. Immunol. 129:2293–2300.PubMedGoogle Scholar
  2. 2.
    Meuer, S. C., Fitzgerald, K. A., Hussey, R. E., Hodgdon, J. C., Schlossman, S. F., and Reinherz, E. L., 1983, Clonotypic structures involved in antigen-specific human T cell function, J. Exp. Med. 157:705–719.PubMedCrossRefGoogle Scholar
  3. 3.
    Acuto, O., Hussey, R. E., Fitzgerald, K. A., Protentis, J. P., Meuer, S. C., Schlossman, S. F., and Reinherz, E. L., 1983, The human T cell receptor: Appearance in ontogeny and biochemical relationship of alpha and beta subunits on IL-2 dependent clones and T cell tumors, Cell 34:717–726.PubMedCrossRefGoogle Scholar
  4. 4.
    Bigler, R. D., Fisher, D. E., Wang, C. Y., Rinnooy Kan, E. A., and Kunkel, H. G., 1983, Idiotypelike molecules on cells of a human T cell leukemia, J. Exp. Med. 158:1000–1005.PubMedCrossRefGoogle Scholar
  5. 5.
    Haskins, K., Kubo, R., White, J., Pigeon, M., Kapler, J., and Marrack, P., 1983, The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody, J. Exp. Med. 157:1149–1169.PubMedCrossRefGoogle Scholar
  6. 6.
    Kaye, J., Porcelli, S., Tite, J., Jones, B., and Janeway, C. A., Jr., 1983, Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells, J. Exp. Med. 158:836–856.PubMedCrossRefGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    Samelson, L. E., Germain, R. N., and Schwartz, R. H., 1983, Monoclonal antibodies against the antigen receptor on a cloned T cell hybrid, Proc. Natl. Acad. Sci. USA 80:6972–6976.PubMedCrossRefGoogle Scholar
  9. 9.
    Staerz, U. D., Pasternack, M. S., Klein, J. R., Benedetto, J. D., and Bevan, M. J., 1984, Monoclonal antibodies specific for a murine cytotoxic T lymphocyte clone, Proc. Natl. Acad. Sci. USA 81:1799–1803.PubMedCrossRefGoogle Scholar
  10. 10.
    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
  11. 11.
    Haskins, K., Hannum, C., White, J., Roehm, N., Kubo, R., Kappler, J., and Marrack, P., 1984, The antigen-specific, major histocompatibility complex-restricted receptor on T cells. VI. An antibody to a receptor allotype, J. Exp. Med. 160:452–471.PubMedCrossRefGoogle Scholar
  12. 12.
    Brenner, M. B., Trowbridge, I. S., McLean, J., and Strominger, J. L., 1984, Identification of shared antigenic determinants of the putative human T lymphocyte antigen receptor, J. Exp. Med. 160:541–551.PubMedCrossRefGoogle Scholar
  13. 13.
    Leonard, W. J., Depper, J. M., Uchiyama, T., Smith, K. A., Waldmann, T. A., and Greene, W. C., 1982, A monoclonal antibody that appears to recognize the receptor for human T cell growth factor; partial characterization of the receptor, Nature 300:267–269.PubMedCrossRefGoogle Scholar
  14. 14.
    Podesta, E. J., Solano, A. R., Attar, R., Sanchez, M. L., and Molina Y Vedia, L., 1983, Receptor aggregation induced by antilutropin receptor antibody and biological response in rat testis Leydig cells, Proc. Natl. Acad. Sci. USA 80:3986–3990.PubMedCrossRefGoogle Scholar
  15. 15.
    Jacobs, S., Chang, K.-J., and Cuatrecasas, P., 1978, Antibodies to purified insulin receptor have insulin-like activity, Science 200:1283–1284.PubMedCrossRefGoogle Scholar
  16. 16.
    Leiber, D., Harbon, S., Guillet, J.-G., Andre, C., and Strosberg, A. D., 1984, Monoclonal antibodies to purified muscarinic receptor display agonist-like activity, Proc. Natl. Acad. Sci. USA 81:4331–4334.PubMedCrossRefGoogle Scholar
  17. 17.
    Schreiber, A. B., Lax, I., Yarden, Y., Eshhar, Z., and Schlessinger, J., 1981, Monoclonal antibodies against receptors for epidermal growth factor induce early and delayed effects of epidermal growth factor, Proc. Natl. Acad. Sci. USA 12:7535–7539.CrossRefGoogle Scholar
  18. 18.
    Sredni, B., and Schwartz, R. H., 1981, Antigen specific proliferating T lymphocyte clones. Methodology, specificity, MHC restriction and alloreactivity, Immunol. Rev. 54:187–223.PubMedCrossRefGoogle Scholar
  19. 19.
    Janeway, C. A., Jr., Lerner, E. A., Conrad, P. J., and Jones, B., 1982, The precision of self and non-self major histocompatibility complex encoded antigen recognition by cloned T cells, Behring Inst. Mitt. 70:200–209.Google Scholar
  20. 20.
    Jones, B., and Janeway, C. A., Jr., 1981, Cooperative interaction of B lymphocytes with antigen-specific helper T lymphocytes is MHC restricted, Nature 292:547–549.PubMedCrossRefGoogle Scholar
  21. 21.
    Bottomly, K., Jones, B., Kaye, J., and Jones, F., III, 1983, Subpopulations of B cells distinguished by cell surface expression of Ia antigens. Correlation of Ia and idiotype during activation by cloned la-restricted T cells, J. Exp. Med. 158:265–279.PubMedCrossRefGoogle Scholar
  22. 22.
    Lerner, E. A., 1981, How to make a hybridoma, Yale J. Biol. Med. 54:387–402.PubMedGoogle Scholar
  23. 23.
    Ey, P. L., Prowse, S. J., and Jenkin, C. R., 1978, Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A Sepharose, Immunochemistry 15:429–436.PubMedCrossRefGoogle Scholar
  24. 24.
    Kaye, J., and Janeway, C. A., Jr., 1984, The Fab fragment of a directly activating monoclonal antibody that precipitates a disulfide-linked heterodimer from a helper T cell clone blocks activation by either allogeneic Ia or antigen and self-la, J. Exp. Med. 159:1397–1412.PubMedCrossRefGoogle Scholar
  25. 25.
    Cantrell, D. A., and Smith, K. A., 1983, Transient expression of interleukin 2 receptors: Consequences for T cell growth, J. Exp. Med. 158:1895–1911.PubMedCrossRefGoogle Scholar
  26. 26.
    Scala, G., Kuang, Y. D., Hall, R. E., Muchmore, A. V., and Oppenheim, J. J., 1984, Accessory cell function of human B cells. I. Production of both interleukin 1-like activity and an interleukin 1 inhibitory factor by an EBV-transformed human B cell line, J. Exp. Med. 159:1637–1652.PubMedCrossRefGoogle Scholar
  27. 27.
    Mizel, S. B., and Ben-Zvi, Amos, 1980, Studies on the role of lymphocyte-activating factor (interleukin 1) in antigen-induced lymph node lymphocyte proliferation, Cell. Immunol. 54:382–389.PubMedCrossRefGoogle Scholar
  28. 28.
    Howard, M., Maus, L., Malek, T. R., Shevach, E., Kell, W., Cohen, D., Nakanishi, K., and Paul, W. E., 1983, Interleukin 2 induces antigen-reactive T cell lines to secrete BCGF-I, J. Exp. Med. 158:2024–2039.PubMedCrossRefGoogle Scholar
  29. 29.
    Inaba, K., Granelli-Pipemo, A., and Steinman, R. M., 1983, Dendritic cells induce T lymphocytes to release B cell-stimulating factors by an interleukin 2-dependent mechanism, J. Exp. Med. 158:2040–2057.PubMedCrossRefGoogle Scholar
  30. 30.
    Kasahara, T., Hooks, J. J., Dougherty, S. F., and Oppenheim, J. J., 1983, Interleukin 2-mediated immune interferon (IFN-7) production by human T cells and T cell subsets, J. Immunol. 130:1784–1789.PubMedGoogle Scholar
  31. 31.
    Neckers, L. M., and Cossman, J., 1983, Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2, Proc. Natl. Acad. Sci. USA 80:3494–3498.PubMedCrossRefGoogle Scholar
  32. 32.
    Tite, J. P., Kaye, J., and Jones, B., 1984, The role of B cell surface Ia antigen recognition by T cells in B cell triggering. Analysis of the interaction of cloned helper T cells with normal B cells in differing states of activation and with B cells expressing the xid defect, Eur. J. Immunol. 14:553–561.PubMedCrossRefGoogle Scholar
  33. 33.
    Smith, K. A., Lachman, L. B., Oppenheim, J. J., and Favata, M. F., 1980, The functional relationship of the interleukins, J. Exp. Med. 151:1551–1556.PubMedCrossRefGoogle Scholar
  34. 34.
    Gillis, S., and Mizel, S. B., 1981, T-cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation, Proc. Natl. Acad. Sci. USA 78:1133–1137.PubMedCrossRefGoogle Scholar
  35. 35.
    Rock, K. R., 1982, The role of Ia molecules in the activation of T lymphocytes. I. The activation of an IL 1-dependent IL 2-producing T cell hybridoma by con A requires an interaction, which is not H-2 restricted, with an la-bearing accessory cell, J. Immunol. 129:1360–1366.PubMedGoogle Scholar
  36. 36.
    Smith, K. A., 1984, Lymphokine regulation of T cell and B cell function, in: Fundamental Immunology (W. E. Paul, ed.), Raven Press, New York, pp. 559–576.Google Scholar
  37. 37.
    Harwell, L., Skidmore, B., Marrack, P., and Kappler, J., 1980, Concanavalin A-inducible, interleukin-2-producing T cell hybridoma, J. Exp. Med. 152:893–904.PubMedCrossRefGoogle Scholar
  38. 38.
    Gillis, S., and Watson, J., 1980, Biochemical and biological characterization of lymphocyte regulatory molecules. V. Identification of an interleukin 2-producing human leukemia T cell line. J. Exp. Med. 152:1709–1719.PubMedCrossRefGoogle Scholar
  39. 39.
    Kaye, J., Gillis, S., Mizel, S. B., Shevach, E. M., Malek, T. R., Dinarello, C. A., Lachman, L. B., and Janeway, C. A., Jr., 1984, Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: Interleukin 1 is required for the expression of receptors for interleukin 2, J. Immunol. 133:1339–1345.PubMedGoogle Scholar
  40. 40.
    Kaye, J., and Janeway, C. A., Jr., 1984, Induction of receptors for interleukin 2 requires T cell Ag:Ia receptor crosslinking and interleukin 1, Lymphokine Res. 3:175–182.PubMedGoogle Scholar
  41. 41.
    Rees Smith, B., Pyle, G. A., Petersen, V. B., Hall, R., 1977, Interaction of thyroid-stimulating antibodies with the human thyrotropin receptor, J. Endocrinol. 75:401–407.CrossRefGoogle Scholar
  42. 42.
    Braun, J., Hochman, P. S., and Unanue, E. R., 1982, Ligand-induced association of surface immunoglobulin and detergent-insoluble cytoskeletal matrix of the B lymphocyte, J. Immunol. 128:1198–1204.PubMedGoogle Scholar
  43. 43.
    Sieckmann, D. G., Asofsky, R., Mosier, D. E., Zitron, I. M., and Paul, W. E., 1978, Activation of mouse lymphocytes by anti-immunoglobulin. I. Parameters of the proliferative response, J. Exp. Med. 147:814–829.PubMedCrossRefGoogle Scholar
  44. 44.
    Fearon, D. T., Kaneko, I., and Thomson, G. G., 1981, Membrane distribution and adsorptive endocytosis by C3b receptors on human polymorphonuclear leukocytes, J. Exp. Med. 153:1615–1628.PubMedCrossRefGoogle Scholar
  45. 45.
    Kasuga, M., Kahn, C. R., Hedo, J. A., Obberghen, E. V., and Yamada, K. M., 1981, Insulin-induced receptor loss in cultured human lymphocytes is due to accelerated receptor degradation, Proc. Natl. Acad. Sci. USA 78:6917–6921.PubMedCrossRefGoogle Scholar
  46. 46.
    Carpenter, G., and Cohen, S., 1976, SPI125I-Labelled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts, J. Cell. Biol. 71:159–171.PubMedCrossRefGoogle Scholar
  47. 47.
    Mellman, I. S., Unkeless, J., Steinman, R. M., and Cohn, Z. A., 1983, Selective internalization and degradation of macrophage Fc receptors during receptor mediated phagocytosis, J. Cell. Biol. 96:887–895.PubMedCrossRefGoogle Scholar
  48. 48.
    Kaye, J., Jones, B., and Janeway, C. A. Jr., 1984, The structure and function of T cell receptor complexes, Immunol. Rev. 81:40–63.CrossRefGoogle Scholar
  49. 49.
    Ways, J. P., and Parham, P., 1983, The binding of monoclonal antibodies to cell surface molecules. A quantitative analysis with immunoglobulin G against two alloantigenic determinants of the human transplantation antigen HLA-A2, Biochem. J. 216:423–432.PubMedGoogle Scholar
  50. 50.
    Medelson, C., Dufau, M., and Catt, K., 1975, Gonadotropin binding and stimulation of cyclic adenosine 3′:5′ monophosphate and testosterone production in isolated Leydig cells, J. Biol. chem. 250:8818–8823.Google Scholar
  51. 51.
    Meuer, S. C., Hodgdon, J. C., Hussey, R. E., Protentis, J. P., Schlossman, S. F., and Reinherz, E. L., 1983, Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones, J. Exp. Med. 158:988–993.PubMedCrossRefGoogle Scholar
  52. 52.
    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
  53. 53.
    Jones, B., 1983, Evidence that the Thy-1 molecule is the target for T cell mitogenic antibody against brain-associated antigens, Eur. J. Immunol. 13:678–684.PubMedCrossRefGoogle Scholar
  54. 54.
    Simonsen, M., 1968, The clonal selection hypothesis evaluated by grafted cells reacting against their hosts, Cold Spring Harbor Symp. Quant. Biol. 32:517–523.CrossRefGoogle Scholar
  55. 55.
    Lindahl, K. F., and Wilson, D. B., 1977, Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors, J. Exp. Med. 145:508–522.PubMedCrossRefGoogle Scholar
  56. 56.
    Kronke, M., Scheurich, P., Pfizenmaier, K., Rollinghoff, M., and Wagner, H., 1982, T-T Cell interactions during in vitro cytotoxic T lymphocyte responses. V. Precursor frequencies and specificity of alloreactive helper T cells, J. Exp. Med. 156:41–54.PubMedCrossRefGoogle Scholar
  57. 57.
    Kaye, J., and Janeway, C. A., Jr., 1984, The α and β subunits of a murine T cell antigen/la receptor have a molecular weight of 31,000 in the absence of N-linked glycosylation, J. Immunol. 135:1–3.Google Scholar
  58. 58.
    Kappler, J., Kubo, R., Haskins, K., Hannum, C., Marrack, P., Pigeon, M., McIntyre, B., Allison, J., and Trowbridge, I., 1983, The major histocompatibility complex-restricted antigen receptor on T cells in mouse and man: Identification of constant and variable peptides, Cell 35:295–302.PubMedCrossRefGoogle Scholar
  59. 59.
    Reinherz, E. L., Meuer, S. C., Fitzgerald, A., Hussey, R. E., Hodgdon, J. C., Acuto, O., and Schlossman, S. F., 1983, Comparison of T3-associated 49- and 43-kilodalton cell surface molecules on individual human T-cell clones: Evidence for peptide variability in T cell receptor structures, Proc. Natl. Acad. Sci. USA 80:4104–4108.PubMedCrossRefGoogle Scholar
  60. 60.
    Chien, Y.-H., Gascogne, N. R. J., Kavaler, J., Lee, N. E., and Davis, M. M., 1984, Somatic recombination in a murine T cell receptor gene, Nature 309:322–326.PubMedCrossRefGoogle Scholar
  61. 61.
    Siu, G., Clark, S. P., Yoshikai, Y., Malissen, M., Yanagi, Y., Strauss, E., Mak, T. W., and Hood, L., 1984, The human T cell antigen receptor is encoded by variable, diversity, and joining gene segments that rearrange to generate a complete V gene, Cell 37:393–401.PubMedCrossRefGoogle Scholar
  62. 62.
    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.PubMedCrossRefGoogle Scholar
  63. 63.
    Saito, H., Kranz, D. M., Takagaki, Y., Hayday, A. C., Eisen, H. N., and Tonegawa, S., 1984, Complete primary structure of a heterodimer T cell receptor deduced from cDNA sequences, Nature 309:757–762.PubMedCrossRefGoogle Scholar
  64. 64.
    Chien, Y., Becker, D. M., Lindsten, T., Okamura, M., Cohen, D. I., and Davis, M. M., 1984, A third type of murine T-cell receptor gene, Nature 312:31–35.PubMedCrossRefGoogle Scholar
  65. 65.
    Saito, H., Kranz, D. M., Takagaki, Y., Hayday, A. C., Eisen, H. N., and Tonegawa, S., 1984, A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes, Nature 312:36–40.PubMedCrossRefGoogle Scholar
  66. 66.
    Deuel, T. F., Huang, J. S., Huang, S. S., Stroobant, P., and Waterfield, M. D., 1983, Expression of a platelet-derived growth factor-like protein in simian sarcoma virus transformed cells, Science 221:1348–1350.PubMedCrossRefGoogle Scholar
  67. 67.
    Downward, J., Yarden, Y., Mayes, E., Scrace, G., Totty, N., Stockwell, P., Ullrich, A., Schlessinger, J., and Waterfield, M. D., 1984, Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences, Nature 307:521–527.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Jonathan Kaye
    • 1
  1. 1.Department of BiologyUniversity of CaliforniaSan Diego, La JollaUSA

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