Skip to main content
SpringerLink
Log in

A hypothetical model of the foreign antigen binding site of Class II histocompatibility molecules

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

An Erratum to this article was published on 23 June 1988

Abstract

Class II and class I histocompatibility molecules allow T cells to recognize 'processed' polypeptide antigens1–5. The two polypeptide chains of class II molecules, α and β, are each composed of two domains (for review see ref. 6); the N-terminal domains of each, α1 and β1, are highly polymorphic6–10 and appear responsible for binding peptides at what appears to be a single site11–13 and for being recognized by MHC-restricted antigen-specific T cells14,15. Recently, the three-dimensional structure of the foreign antigen binding site of a class I histocompatibility antigen has been described16,17. Because a crystal structure of a class II molecule is not available, we have sought evidence in class II molecules for the structural features observed in the class I binding site by comparing the patterns of conserved and polymorphic residues of twenty-six class I and fifty-four class II amino acid sequences. The hypothetical class II foreign-antigen binding site we present is consistent with mutation experiments18–28 and provides a structural framework for proposing peptide binding models to help understand recent peptide binding data11,29–33.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Benacerraf, B. J. Immun. 120, 1809–1812 (1978).

    CAS  PubMed  Google Scholar 

  2. Rock, K. L. & Benacerraf, B. J. exp. Med. 159, 1238–1252 (1984).

    Article  CAS  PubMed  Google Scholar 

  3. Ziegler, H. K. & Unanue, E. R. Proc natn. Acad. Sci. U.S.A. 79, 175–178 (1982).

    Article  ADS  CAS  Google Scholar 

  4. Shimonkevitz, R., Kappler, J., Marrack, P. & Grey, H. J. exp. Med. 158, 303–316 (1983).

    Article  CAS  PubMed  Google Scholar 

  5. Townsend, A. R. M., Gotch, F. M. & Davey, J. Cell 42, 457–468 (1985).

    Article  CAS  PubMed  Google Scholar 

  6. Kaufman, J. F., Auffray, C., Korman, A. J., Shackelford, D. A. & Strominger, J. L. Cell 36, 1–13 (1984).

    Article  CAS  PubMed  Google Scholar 

  7. Benoist, C. O., Mathis, D. J., Kanter, M. R., Williams II, V. E. & McDevitt, H. O. Cell 34, 169–177 (1983).

    Article  CAS  PubMed  Google Scholar 

  8. Choi, E., McIntyre, K., Germain, R. N. & Seidman, J. G. Science 221, 283–286 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  9. Larhammer, D. et al. Cell 34, 179–188 (1983).

    Article  Google Scholar 

  10. Schenning, L. et al. EMBO J. 3, 447–452 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Guillet, J-G. et al. Science 235, 865–870 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Buus, S., Sette, A., Colon, S. M., Miles, C. & Grey, H. M. Science 235, 1353–1358 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Babbitt, B. P., Allen, P. M., Matsueda, G., Haber, E. & Unanue, E. R. Nature 317, 359–360 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Folsom, V., Gay, D. & Tonegawa, S. Proc. natn. Acad. Sci. U.S.A. 82, 1678–1682 (1985).

    Article  ADS  CAS  Google Scholar 

  15. Germain, R. N. et al. Proc. natn. Acad. Sci. U.S.A. 82, 2940–2944 (1985).

    Article  ADS  CAS  Google Scholar 

  16. Bjorkman, P. J. et al. Nature 329, 506–512 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Bjorkman, P. J. et al. Nature 329, 512–518 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Landais, D. et al. Cell 47, 173–181 (1986).

    Article  CAS  PubMed  Google Scholar 

  19. Griffith, I. J., Choi, E. M. & Glimcher, L. H. Proc. natn. Acad. Sci. U.S.A. 84, 1090–1093 (1987).

    Article  ADS  CAS  Google Scholar 

  20. Cohn, L. E. et al. Proc. natn. Acad. Sci. U.S.A. 83, 747–751 (1986).

    Article  ADS  CAS  Google Scholar 

  21. Buerstedde, J.-M. et al. J. exp. Med. (in the press).

  22. Ronchese, F., Schwartz, R. H. & Germain, R. N. Nature 329, 254–256 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Quill, H., Schwartz, R. H. & Glimcher, L. H. J. Immun. 136, 3351–3359 (1986).

    CAS  PubMed  Google Scholar 

  24. Griffith, I. J., Carland, F. M. & Glimcher, L. H. J. Immun. 138, 4480–4483 (1987).

    CAS  PubMed  Google Scholar 

  25. Beck, B. N. et al. J. exp. Med. 166, 433–443 (1987).

    Article  CAS  PubMed  Google Scholar 

  26. Beck, B. N., Glimcher, L. H., Nilson, A. E., Pierres, M. & McKean, D. J. J. Immun. 133, 3176–3181 (1984).

    CAS  PubMed  Google Scholar 

  27. Brown, M. A., Glimcher, L. H., Nielsen, E. A., Paul, W. E. & Germain, R. N. Science 231, 255–258 (1986).

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Ronchese, F., Brown, M. A. & Germain, R. N. J. Immun. 139, 629–638 (1987).

    CAS  PubMed  Google Scholar 

  29. Babbitt, B. P., Matsueda, G., Haber, E., Unanue, F., R. & Allen, P. M. Proc. natn. Acad. Sci. U.S.A. 4509–4513 (1986).

  30. Buus, S., Sette, A., Colon, S. M., Jenis, D. M. & Grey, H. M. Cell 47, 1071–1077 (1986).

    Article  CAS  PubMed  Google Scholar 

  31. Allen, P. M. et al. Nature 327, 713–715 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  32. Sette, A., Buus, S., Colon, S., Smith, J. A., Miles, C. & Grey, H. M. Nature 328, 395–399 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  33. Fox, B. S. et al. J. Immun. 139, 1578–1588 (1987).

    CAS  PubMed  Google Scholar 

  34. Travers, P., Blundell, T. L., Sternberg, M. J. E. & Bodmer, W. Nature 310, 235–238 (1984).

    Article  ADS  CAS  PubMed  Google Scholar 

  35. Rupp, F., Acha-Orbea, H., Hengartner, H., Zinkernagel, R. & Joho, R. Nature 315, 425–427 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  36. Marrack, P. & Kappler, F. Adv. Immun. 38, 1–30 (1986).

    Article  CAS  PubMed  Google Scholar 

  37. Braunstein, N. S. & Germain, R. N. Proc. natn. Acad. Sci. U.S.A. 84, 2921–2925 (1987).

    Article  ADS  CAS  Google Scholar 

  38. Sant, A. J., Braunstein, N. S. & Germain, R. N. Proc. natn. Acad. Sci. U.S.A. 84, 8065–8069 (1987).

    Article  ADS  CAS  Google Scholar 

  39. Korman, A. J., Auffray, C., Schamboeck, A. & Strominger, J. L. Proc. natn. Acad. Sci. U.S.A. 79, 6013–6017 (1982).

    Article  ADS  CAS  Google Scholar 

  40. Larhammer, D. et al. Proc. natn. Acad. Sci. U.S.A. 79, 3687–3691 (1982).

    Article  ADS  Google Scholar 

  41. Travers, P., thesis, Univ. London (1984).

  42. Hood, L., Steinmetz, M. & Malissen, B. A. Rev. Immun. 1, 529–568 (1983).

    Article  CAS  Google Scholar 

  43. Nathenson, S. G., Geliebter, J., Pfaffenbach, G. M. & Zeff, R. A. A. Rev. Immun. 4, 471–502 (1986).

    Article  CAS  Google Scholar 

  44. Michaelides, M., Sandrin, M., Morgan, G., McKenzie, I. F. C., Ashman, R. & Melvold, R.W. J. exp. Med. 153, 464–469 (1981).

    Article  CAS  PubMed  Google Scholar 

  45. Gussow, D. et al. Immunogenetics 25, 313–322 (1987).

    Article  CAS  PubMed  Google Scholar 

  46. Richardson, J. S., Getzoff, E. D. & Richardson, D. C. Proc. natn. Acad. Sci. U.S.A. 75, 2574–2578 (1978).

    Article  ADS  CAS  Google Scholar 

  47. Auffray, C. & Novotny, J. Hum. Immun. 15, 381–390 (1986).

    Article  CAS  PubMed  Google Scholar 

  48. Heber-Katz, E., Hansburg, D. & Schwartz, R. H. J. Molec. cell. Immun. 1, 3–14 (1983).

    CAS  Google Scholar 

  49. Todd, J. A., Bell, J. I. & McDevitt, H. O. Nature 329, 599–604 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  50. Horn, G. T., Bugawan, T. L., Long, C. M. & Erlich, H. A. Proc. natn. Acad. Sci. U.S.A. (in the press).

  51. Amit, A. G., Mariuzza, R. A., Phillips, S. E. V. & Poljak, R. J. Science 233, 747–753 (1986).

    Article  ADS  CAS  PubMed  Google Scholar 

  52. Colman, P. M. et al. Nature 326, 358–363 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  53. Sheriff, S. et al. Proc. natn. Acad. Sci. U.S.A. 84, 8075–8079 (1987).

    Article  ADS  CAS  Google Scholar 

  54. Hedrick, S. M., Nielsen, E. A., Kavaler, J., Cohen, D. I. & Davis, M. M. Nature 308, 253–258 (1984).

    Google Scholar 

  55. Wu, T. T. & Kabat, E. A. J. exp. Med. 132, 211–250 (1970).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lesk, A. M. & Chothia, C. J. molec. Biol. 136, 225–270 (1980).

    Article  CAS  PubMed  Google Scholar 

  57. Kuntz, I. D. J. Am. chem. Soc. 93, 516–518 (1971).

    Article  CAS  PubMed  Google Scholar 

  58. Cowan, E. P., Jelachich, M. L., Biddison, W. E. & Coligan, J. E. Immunogenetics 25, 241–250 (1987).

    Article  CAS  PubMed  Google Scholar 

  59. Immunology Today, Centre-page Diagram, Ref. No. 13 (Elsevier, Cambridge, U.K.).

  60. Bell, J. I. et al. Proc. natn. Acad. Sci. U.S.A. 84, 6234–6238 (1987).

    Article  ADS  CAS  Google Scholar 

  61. Ayane, M., Mengle-Gaw, L., McDevitt, H. O., Benoist, C. & Mathis, D. J. Immun. 137, 948–951 (1986).

    CAS  PubMed  Google Scholar 

  62. Landais, D., Matthes, H., Benoist, C. & Mathis, D. Proc. natn. Acad. Sci. U.S.A. 82, 2930–2934 (1985).

    Article  ADS  CAS  Google Scholar 

  63. Estess, P., Begovich, A. B., Koo, M., Jones, P. P. & McDevitt, H. O. Proc. natn. Acad. Sci. U.S.A. 83, 3594–3598 (1986).

    Article  ADS  CAS  Google Scholar 

  64. Schiffenbauer, J. et al. J. Immun. 139, 228–233 (1987).

    CAS  PubMed  Google Scholar 

  65. Jonsson, A. et al. J. biol. Chem. 262, 8767–8777 (1987).

    CAS  PubMed  Google Scholar 

  66. Korman, A. J. et al. Immun. Rev. 85, 45–86 (1985).

    Article  CAS  PubMed  Google Scholar 

  67. Kappes, D. & Strominger, J. L. A. Rev. Biochem. 57 (in the press).

  68. Lesk, A. M. & Chothia, C. J. molec. Biol. 160, 325–342 (1982).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Pamela J. Bjorkman

    Present address: Department of Medical Microbiology, Stanford University, Stanford, California, 94305, USA

  2. Don C. Wiley: To whom correspondence should be addressed.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Harvard University, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, 02138, USA

    Jerry H. Brown, Theodore Jardetzky, Mark A. Saper, Boudjema Samraoui, Pamela J. Bjorkman & Don C. Wiley

  2. Department of Medical Microbiology, Stanford University, Stanford, California, 94305, USA

    Pamela J. Bjorkman

Authors
  1. Jerry H. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Theodore Jardetzky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark A. Saper
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Boudjema Samraoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pamela J. Bjorkman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Don C. Wiley
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brown, J., Jardetzky, T., Saper, M. et al. A hypothetical model of the foreign antigen binding site of Class II histocompatibility molecules. Nature 332, 845–850 (1988). https://doi.org/10.1038/332845a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/332845a0

  • Springer Nature Limited

This article is cited by

Search

Navigation