The Major Histocompatibility Complex and Protein Recognition by T Lymphocytes

  • Jan Klein
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 225)


In biochemistry all good things come in twos -- as pairs of receptors and their ligands (Fig. 1). An enzyme interacts with its substrate and thus initiates or accelerates a chemical reaction. A hormone binds to its receptor and thus regulates a physiological process. A regulatory protein attaches to a promoter region of DNA and thus activates a gene. And so on. In immunology, on the other hand, the best things come in threes. Here, the T-cell receptor (Tcr) curiously enough does not react with one but with two ligands simultaneously: with an antigen and with major histocompatibility complex (Mhc) molecules (Fig. 2). The immune system, to be sure, has not completely abandoned the old-fashioned twosome relationship (antibodies react with antigens and antigens only), but the most profound event in the immune response, the initial distinction between self and non-self, is a threesome affair.


Major Histocompatibility Complex Blind Spot Nominal Antigen Lymphocytic Choriomeningitis Nonresponder Individual 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Babbitt, B. P., Allen, P. M., Matsueda, G., Haber, E., and Unanue, E. R., 1985, Binding of immunogenic peptides to la histocompatibility molecules. Nature 317: 359.PubMedCrossRefGoogle Scholar
  2. Babbitt, B. P., Matsueda, G., Haber, E., Unanue, E. R., and Allen, P. M., 1986, Antigenic competition at the level of peptide-Ia binding. Proc. Natl. Acad. Sci. USA 83: 5509.CrossRefGoogle Scholar
  3. Baxevanis, C. N., Wernet, D., Nagy, Z. N., Maurer, P. H., and Klein, J., 1980, Genetic control of T-cell proliferative responses to poly(Glu40 Ala60) and poly(Glu5Lys34Tyr15): Subregion-specific inhibition of the responses with monoclonal la antibodies. Immunogenetics 11: 617.PubMedCrossRefGoogle Scholar
  4. Carel, S., Bron, C., and Corradin, G., 1983, T-cell hybridome specific for a cytochrome c peptide: specific antigen binding and interleukin 2 production. Proc. Natl. Acad. Sci. USA 80: 4832.PubMedCrossRefGoogle Scholar
  5. Corradin, G., and Engers, H. D., 1984, Inhibition of antigen-induced T-cell clone proliferation by antigen-specific antibodies. Nature 308: 547.PubMedCrossRefGoogle Scholar
  6. Grey, H. M., and Chesnut, R., 1985, Antigen processing and presentation to T cells. Immunol. Today 6: 101.CrossRefGoogle Scholar
  7. Ishii, N., Baxevanis, C. N., Nagy, Z. A., and Klein, J., 1981, Responder T cells depleted of alloreactive cells react to antigen presented on allogeneic macrophages from nonresponder strains. J. Exp. Med. 154: 978.PubMedCrossRefGoogle Scholar
  8. Ishii, N., Nagy, Z. A., and Klein, J., 1982a, Absence of Ir gene control of T cells recognizing foreign antigen in the context of allogeneic MHC molecules. Nature 295: 531.PubMedCrossRefGoogle Scholar
  9. Ishii, N., Nagy, Z. A., and Klein, J., 1982b, Restriction molecules involved in the interaction of T cells with allogeneic antigen-presenting cells. J. Exp. Med. 156: 622.PubMedCrossRefGoogle Scholar
  10. Ishii, N., Nagy, Z. A., and Klein, J., 1983, In vitro correlate for a clonal deletion mechanism of immune response gene-controlled nonresponsiveness. J. Exp. Med. 157: 998.PubMedCrossRefGoogle Scholar
  11. Kast, W. M., de Waal, L. P., and Melief, C. M., 1984, The thymus dictates MHC specificity and Ir gene phenotype of T cells restricted to class II MHC molecules but not of T cells restricted to class I MHC molecules. J. Exp. Med. 160: 1752.PubMedCrossRefGoogle Scholar
  12. Klein, J., 1984, What causes immunological nonresponsiveness? Immunol. Rev. 81: 177.PubMedCrossRefGoogle Scholar
  13. Klein, J., 1986, “Natural History of the Major Histocompatibility Complex,” Wiley, New York.Google Scholar
  14. Klein, J., and Nagy, Z. A., 1982, Mhc restriction and Ir genes, in “Advances in Cancer Research,” Vol. 37, Academic Press, New York.Google Scholar
  15. Klein, J., and Walden, P., 1986, Antigen presentation: Paradigm lost?, in “Immunology 1986,” B. Cinader and R.G. Miller, eds., in press.Google Scholar
  16. Klein, J., Walden P., and Nagy, Z. A., 1985, Antigen processing: A reevalua- tion, in “Immune Regulation,” M. Feldman and N. A. Mitchison eds., The Humana Press, Clifton, New Jersey.Google Scholar
  17. Kovac, Z., and Schwartz, R. H., 1985, The molecular basis of the requirement for antigen processing of pigeon cytochrome c prior to T cell activation. J. Immunol. 134: 3233.PubMedGoogle Scholar
  18. Lamb, J. R., Zanders, E. D., Lake, P., Webster, R. G., Eckels, D. D., Woody, J. N., Green, N., Lerner, R. A., Feldmann, M., 1984, Inhibition of T cell proliferation by antibodies to synthetic peptides. Eur. J. Immunol. 14: 153.PubMedCrossRefGoogle Scholar
  19. Lerner, L. A., Matis, L. A., Janeway, Jr., C. A., Jones, P. P., Schwartz, R. H., and Murphy, D. B., 1980, Monoclonal antibody against an Ir gene product? J. Exp. Med. 152: 1085.PubMedCrossRefGoogle Scholar
  20. Nagy, Z. A., Baxevanis, C. N., Ishii, N., and Klein, J., 1981, la antigens as restriction molecules in Ir-gene controlled T-cell proliferation. Immunol. Rev. 60: 59PubMedCrossRefGoogle Scholar
  21. Ohno, S., Epplen, J. T., and Suton, S., 1981, Testis-organizing H-Y antigen as a discrete protein: its MHC restricted immune recognition and the genomic environment in which H-Y gene operates. Hum. Genet. 58: 37.PubMedCrossRefGoogle Scholar
  22. Phillips, M. L., Moule, M. L., Delovitch, T. L., and Yip, C. C., 1986, Class I histocompatibility antigens and insulin receptors: evidence for interactions. Proc. Natl. Acad. Sci. USA 83: 3474.PubMedCrossRefGoogle Scholar
  23. Rao, A., Ko. W. W.-P., Faas, S. J., and Cantor, H., 1984a, Binding of antigen in the absence of histocompatibility proteins by arsonatereactive T-cell clones. Cell 36: 879.PubMedCrossRefGoogle Scholar
  24. Rao, A., Faas, S. J., and Cantor, H., 1984b, Analogs that compete for antigen binding to arsonate-reactive T-cell clones inhibit the functional response to arsonate. Cell 36: 889.PubMedCrossRefGoogle Scholar
  25. Sherman, L.A., 1982, Recognition of conformational determinants on H-2 by cytolytic T lymphocytes. Nature 297: 511.PubMedCrossRefGoogle Scholar
  26. Siliciano, R. F., Keegan, A. D., Dintzis, R.Z., Dintzis, H. M., and Shin, H. S., 1985a, The interaction of nominal antigen with T cell antigen receptors. I. Specific binding of multivalent nominal antigen to cytolytic T cell clones. J. Immunol. 135: 906.PubMedGoogle Scholar
  27. Siliciano, R. F., Colello, R. M., Keegan, A. D., Dintzis, R. Z., Dintzis, H. M., and Shin, H. S., 1985b, Antigen valence determines the binding of nominal antigen to T cell clones. J. Exp. Med. 162: 768.PubMedCrossRefGoogle Scholar
  28. Siliciano, R. F., Hemesath, T. J., Pratt, J. C., Dintzis, R. Z., Dintzis, H. M., Acuto, O., Shin, H. S., and Reinherz, E. L., 1986, Direct evidence for the existence of nominal antigen binding sites on T cell surface Ti a-ß heterodimers of MHC-restricted T cell clones. Cell 471: 161.CrossRefGoogle Scholar
  29. Streicher, Z., Berkower, I. J., Busch, M., Gurd, F. R. N., and Berzofsky, J. A., 1984, Antigen conformation determines processing requirements for T-cell activation. Proc. Natl. Acad. Sci. USA 81: 6831.PubMedCrossRefGoogle Scholar
  30. Vidovie, D., Klein, J., and Nagy, Z. A., 1985, Recessive T cell response to poly(Glu50 Tyr50) possibly caused by self tolerance. J. Immunol. 134: 3563.Google Scholar
  31. Vucak, I., Raska, K., Nagy, Z. A., and Klein, J., 1983, Frequency of responsiveness to the H-Y antigen among the B10.W lines. J. Immunol. 131: 325.PubMedGoogle Scholar
  32. Walden, P. Nagy, Z. A., and Klein, J., 1985, Induction of regulatory T-lymphocyte responses by liposomes carrying major histocompatibility complex molecules and foreign antigen. Nature 315: 6017.Google Scholar
  33. Walden, P., Nagy, Z. A., and Klein, J., 1986a, Antigen presentation by liposomes: inhibition with antibodies. Eur. J. Immunol. 16: 717.PubMedCrossRefGoogle Scholar
  34. Walden, P., Nagy, Z. A., and Klein, J., 1986b, Major histocompatibility complex-restricted and unrestricted activation of helper T cell lines by liposome-bound antigens. J. Mol. Cell. Biol. 2: 191.Google Scholar
  35. Zinkernagel, R. M., and Doherty, P. C., 1974, Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature, 248: 701.PubMedCrossRefGoogle Scholar
  36. Zinkernagel, R.M., Callahan, G. N., Althage, A., Cooper, S., Klein P. A., and Klein, J., 1978, On the thymus in the differentiation of “H-2 self recognition” by T cells: Evidence for dual recognition? J. Exp. Med. 147: 882.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Jan Klein
    • 1
  1. 1.Abteilung ImmungenetikMax-Planck-Institut für BiologieTübingenFederal Republic of Germany

Personalised recommendations