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A Model for T Cell Receptor and MHC/Peptide Interaction

  • Mark M. Davis
  • Pamela J. Bjorkman

Abstract

For some time it has been known that T cell recognition of antigen occurs in an MHC restricted fashion (1–3). Much recent evidence suggests that the antigens ‘seen’ by T cell receptors (TcR) are fragments (presumably derived by intracellular processing) bound to MHC molecules at a single site (4–10) By contrast, the immunoglobulin (Ig) B cell receptor can bind to native antigen alone. Structurally and genetically however, both immunoglobulins and T cell receptors seem very similar. Both are derived from the relatively random juxtaposition of different coding segments (V, D and J) of DNA to produce proteins that differ in their N-terminal domains (V-domains), but are the same elsewhere (C domains) (11–13). Ig V region domains from the heavy and light chain polypeptides (VH and VL) pair to form the ligand binding region (14). By analogy, it seems likely that the binding site for antigen and MHC is formed by pairs of TcR V-domains (either α:β or γ: δ). In the Ig variable regions, sequence diversity is concentrated in three distinct ‘hypervariable regions’(15, 16). These amino acids form the principal points of contact with antigens and are thus referred to as complementarity determining regions (CDR’s) (17, 18).

Keywords

Complementarity Determine Region Antigen Binding Site Howard Hughes Medical Institute Ligand Binding Region Versus Gene Segment 
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.
    D. H. Katz, T. Hamaoka, and B. Benacerraf. Cell interactions between histoincompatible T and B lymphocytes. II. Failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugates. J. Exp. Med. 137: 1405 (1973).PubMedCrossRefGoogle Scholar
  2. 2.
    A. S. Rosenthal, and E. M. Shevach. Function of macrophages in antigen recognition by guinea pig T lymphocytes. J. Exp. Med. 138: 1194 (1973).PubMedCrossRefGoogle Scholar
  3. 3.
    R. M. Zinkernagel, and P. C. Doherty. Restriction of in vitro T-cell mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semi-allogeneic system. Nature 248: 701 (1974).PubMedGoogle Scholar
  4. 4.
    B. Benacerraf. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J. Immunol. 120: 1809 (1978).PubMedGoogle Scholar
  5. 5.
    R. Shimonkevitz, J. W. Kappler, P. Marrack, and H. M. Grey. Antigen recognition by H-2 restricted T cells. I. Cell free antigen processing. J. Exp. Med. 158: 303 (1983).PubMedCrossRefGoogle Scholar
  6. 6.
    B. P. Babbitt, P. M. Allen, G. Matsueda, E. Haber, and E. R. Unanue. Binding of immunogenic peptides to la histocompatibility molecules. Nature 317: 359 (1985).Google Scholar
  7. 7.
    S. Buus, S. Colon, C. Smith, J.H. Freed, C. Miles, and H. M. Grey. Interaction between a “processed” ovalbumin peptide and la molecules. Proc. Natl. Acad. Sci. USA 83: 3968 (1986).CrossRefGoogle Scholar
  8. 8.
    A. R. M. Townsend, J. Rothbard, G. M. Gotch, G. Bahadur, D. Wraith, and A. J. McMichael. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44: 959 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    J-G. Guillet, M-Z. Lai, T. J. Briner, J. A. Smith, and M. L. Gefter. Interaction of peptide antigens and class II major histocompatibility complex antigens. Nature 324: 260 (1986).Google Scholar
  10. 10.
    P. J. Bjorkman, M. A. Saper, B. Samraoui, W. S. Bennett, J. L. Strominger, and D. C. Wiley. Structure of the human class I histocompatibility antigen, HLAL-A2. Nature 329: 506 (1987).PubMedCrossRefGoogle Scholar
  11. 11.
    S. Tonegawa. Somatic generation of antibody diversity. Nature 302: 575 (1983).Google Scholar
  12. 12.
    M. Kronenberg, G. Sui, L. E. Hood, and N. Shastri. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Ann. Rev. Immunol. 4: 529 (1986).Google Scholar
  13. 13.
    M. M. Davis, and P. J. Bjorkman. T cell antigen receptor genes and T cell recognition. Nature 334: 395 (1988).Google Scholar
  14. 14.
    H. N. Eisen. “Immunology,” Harper & Row, New York, (1980).Google Scholar
  15. 15.
    T. T. Wu, and E. A. Kabat. Analysis of the sequences of the variable regions of Bence-Jones proteins and myeloma light chains and their implications for antibody complementarity. J. Exp. Med. 132: 211 (1970).PubMedCrossRefGoogle Scholar
  16. 16.
    E. A. Kabat, T. T. Wu, M. Reid-Miller, H. M. Perry, and K. S. Gottesman. “Sequences of Proteins of Immunological Interest”, Public Health Service, NIH, Bethesda, Maryland, 1987.Google Scholar
  17. 17.
    L. M. Amzel, and R. J. Poljak. Three-dimensional structure of immunoglobulins. Ann. Rev. Biochem. 48: 961 (1979).PubMedCrossRefGoogle Scholar
  18. 18.
    D. R. Davies, and H. Metzger. Structural basis of antibody function. Ann. Rev. Immunol. 1: 87 (1983).CrossRefGoogle Scholar
  19. 19.
    P. Patten, T. Yokota, J. Rothbard, Y. Chien, K. Arai, and M. M. Davis. Structure, expression and divergence of T cell receptor beta-chain variable regions. Nature 312: 40 (1984).Google Scholar
  20. 20.
    R. Barth, B. Kim, N. Lan, T. Hunkapiller, N. Sobieck, A. Winoto, H. Gershenfeld, C. Okada, D. Hansburg, I. Weissman, and L. Hood. The murine T-cell receptor uses a limited repertoire of expressed Vb gene segments. Nature 316: 517 (1985).Google Scholar
  21. 21.
    B. Arden, J. Klotz, G. Sui, and L. Hood. Diversity and structure of genes of the alpha family of mouse T-cell antigen receptor. Nature 316: 783 (1985).Google Scholar
  22. 22.
    D. M. Becker, P. Patten, Y. Chien, T. Yokota, Z. Eshhar, M. Giedlin, N. R. J. Gascoigne, C. Goodnow, R. Wolf, K. Arai, and M. M. Davis. Variability and repertoire size in T cell receptor V and Vß gene segments. Nature 317: 430 (1985).Google Scholar
  23. 23.
    S. M. Hedrick, E. A. Nielsen, J. Kavaler, D. I. Cohen, and M. M. Davis. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature 308: 153 (1984).Google Scholar
  24. J. Novotny, S. Tonegawa, H. Saito, D. M. Kranz, and H. N. Eisen. Secondary, tertiary, and quaternary structure of T-cell-specific immunoglobulin-like polypeptide chains. Proc. Natl. Acad. Sci. USA 83:742 (1986).Google Scholar
  25. 25.
    C. Chothia, and A. M. Lesk. Canonical structures for the hypervariable regions of immunoglobulins. J. Mol. Biol. 196: 901 (1987).CrossRefGoogle Scholar
  26. 26.
    J. Novotny, and E. Haber. Structural invariants of antigen binding: Comparisons of immunoglobulin VL-V and V -V domain dimers. Proc. Natl. Acad. Sci. USA 8: 4592 1985 ).CrossRefGoogle Scholar
  27. 27.
    C. Chothia, J. Novotny, R. Bruccoleri, and M. Karplus. Domain association in immunoglobulin molecules. The packing of variable domains. J. Mol. Biol. 186: 651 (1985).PubMedCrossRefGoogle Scholar
  28. 28.
    A. G. Amit, R. A. Mariuzza, S. E. V. Phillips, and R. J. Poljak. Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science 233: 7474 (1986).CrossRefGoogle Scholar
  29. 29.
    P. M. Colman, W. G. Laver, J. N. Varghese, A. T. Baker, P. A. Tulloch, G. M. Air, and R. G. Webster. Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature 326: 358 (1987).Google Scholar
  30. 30.
    S. Sheriff, E. W. Silverton, E. A. Padlan, G. H. Cohen, S. J. Smith-Gill, B. C. Finzel, and D. R. Davies. Three-dimensional structure of an antibody-antigen complex. Proc. Natl. Acad. Sci. USA 84: 8075 (1987).CrossRefGoogle Scholar
  31. 31.
    D. M. Segal, E. A. Padlan, G. H. Cohen, S. Rudikoff, M. Potter, and D. R. Davies. The three-dimensional structure of a phyosphorylcholine-binding mouse immunoglobulin Fab and the nature of the antigen binding site. Proc. Natl. Acad. Sci. USA 71: 4298 (1974).PubMedCrossRefGoogle Scholar
  32. 32.
    P. J. Bjorkman, M. A. Saper, B. Samraoui, W. S. Bennett, J. L. Strominger, and D. C. Wiley. The foreign antigen binding site and T cell recognition regions of Class I histocompatibility antigens. Nature 329: 512 (1987).Google Scholar
  33. 33.
    J. F. Elliott, E. P. Rock, P. A. Patten, M. M. Davis, and Y. Chien. The adult T-cell receptor 8 -chain is diverse and distinct from that of fetal thymocytes. Nature 331: 627 (1988).PubMedCrossRefGoogle Scholar
  34. 34.
    Y. Chien, M. Iwashima, D. A. Wettstein, K. B. Kaplan, J. F. Elliott, W. Born, and M. M. Davis. T-cell receptor d gene rearrangements in early thymocytes. Nature 330: 722 (1987).Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Mark M. Davis
    • 1
    • 2
  • Pamela J. Bjorkman
    • 2
  1. 1.The Howard Hughes Medical InstituteStanford University School of MedicineStanfordUSA
  2. 2.Department of Medical MicrobiologyStanford University School of MedicineStanfordUSA

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