Binding of immunogenic peptides to Ia histocompatibility molecules (original) (raw)

Nature volume 317, pages 359–361 (1985)Cite this article

Abstract

Most cellular interactions essential for the development of an immune response involve the membrane glycoproteins encoded in the major histocompatibility gene complex1–3. The products of the I region, the class II histocompatibility molecules (Ia molecules), are essential for accessory cells such as macrophages to present polypeptide antigens to helper T cells. This interaction, antigen presentation, is needed for T-cell recognition of the antigen and its consequent activation. How the Ia molecules regulate the immune response during antigen presentation is not known, although it is commonly thought to result from their association with the presented antigen1,4,5. Recent studies, including the elucidation of the structure of the T-cell receptor, favour recognition of a single structure, an antigen–Ia complex6–8. Here we report attempts to determine whether purified Ia glycoproteins have an affinity for polypeptide antigens presented by intact cells in an Ia-restricted manner. We first identified the epitope of a peptide antigen involved in presentation9. Several laboratories have shown that globular proteins are altered (processed) in intracellular vesicles of the antigen-presenting cell before antigen presentation10–12. A major component of the T-cell response is directed toward determinants found in the unfolded or denatured molecule, and our laboratory has shown that the determinant of the hen-egg lysozyme protein (HEL), presented in H–2k mice to T cells, is a sequence of only 10 amino acids9. This portion resides in an area of the native molecule partially buried inside the molecule, in a _β_-sheet conformation. To be presented, intact or native HEL must first be processed in acidic intracellular vesicles12. Having isolated the peptide responsible for T-cell recognition of HEL, we sought a physical association of this peptide with purified, detergent-solubilized I–Ak molecules from B-hybridoma cells. We have found such an association, which may explain the role of the Ia glycoproteins in cellular interactions.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Schwartz, R., Yano, A., Stimpfling, J. & Paul, W. J. exp. Med. 149, 40–57 (1979).
    Article CAS Google Scholar
  2. Unanue, E. R. Adv. Immun. 31, 1–135 (1981).
    Article CAS Google Scholar
  3. Rosenthal, A. S. & Shevach, E. M. J. exp. Med. 138, 1194–1212 (1973).
    Article CAS Google Scholar
  4. Schwartz, R. in Fundamental Immunology, 379–438 (Raven, New York, 1984).
    Google Scholar
  5. Benacerraf, B. J. Immun. 120, 1809–1812 (1978).
    CAS Google Scholar
  6. Kappler, J. B., Skidmore, B., White, J. & Marrack, P. J. exp. Med. 153, 1198–1214 (1981).
    Article CAS Google Scholar
  7. Patten, P. et al. Nature 312, 40–46 (1984).
    Article ADS CAS Google Scholar
  8. Chien, Y.-H. et al. Nature 312, 31–35 (1984).
    Article ADS CAS Google Scholar
  9. Allen, P. M., Matsueda, G. R., Haber, E. & Unanue, E. R. J. Immun. 135, 368–373 (1985).
    CAS PubMed Google Scholar
  10. Ziegler, H. K. & Unanue, E. R. Proc. natn. Acad. Sci. U.S.A. 79, 175–178 (1982).
    Article ADS CAS Google Scholar
  11. Chesnut, R., Endres, R. & Grey, H. M. Clin. Immun. Immunopath. 15, 397–408 (1980).
    Article CAS Google Scholar
  12. Allen, P. M. & Unanue, E. R. J. Immun. 132, 1077–1079 (1984).
    CAS PubMed Google Scholar
  13. Aboderin, A. A., Boedefeld, E. & Luisi, P. L. Biochim. biophys. Acta 328, 20–30 (1973).
    Article CAS Google Scholar
  14. Turkewitz, A. P., Sullivan, C. P. & Mescher, M. P. Molec. Immun. 20, 1139–1147 (1983).
    Article CAS Google Scholar
  15. Glimcher, L. H., Schroer, J. A., Chan, C. & Shevach, E. M. J. Immun. 131, 2868–2874 (1983).
    CAS PubMed Google Scholar
  16. Watts, T. H., Brian, A. A., Kappler, J. W., Marrack, P. & McConnell, H. M. Proc. natn. Acad. Sci. U.S.A. 81, 7564–7568 (1984).
    Article ADS CAS Google Scholar
  17. Shimonkevitz, R., Colon, S., Kappler, J. W., Marrack, P. & Grey, H. M. J. Immun. 133, 2067–2074 (1984).
    CAS PubMed Google Scholar
  18. Clark, R., Chiba, J., Zweig, S. & Shevach, E. Nature 295, 412 (1982).
    Article ADS CAS Google Scholar
  19. Hansburg, D., Heber-Katz, E., Fairwell, T. & Appella, E. J. exp. Med. 158, 25–39 (1983).
    Article CAS Google Scholar
  20. Rock, K. L. & Benacerraf, B. J. exp. Med. 157, 1618–1634 (1983).
    Article CAS Google Scholar
  21. Werdelin, O. J. Immunology 129, 1883–1891 (1982).
    CAS Google Scholar
  22. Frelinger, J. G. et al. J. exp. Med. 159, 704–715 (1984).
    Article CAS Google Scholar
  23. Glimcher, L. H., Serog, B., McKane & Beck, B. N. J. Immun. 134, 1780–1786 (1985).
    CAS PubMed Google Scholar
  24. Pierres, M., Devaux, C., Dosseto, M. & Marchetto, S. Immunogenetics 14, 481 (1981).
    Article CAS Google Scholar
  25. Allen, P. M., Strydom, D. J. & Unanue, E. R. Proc. natn. Acad. Sci. U.S.A. 81, 2489–2493 (1984).
    Article ADS CAS Google Scholar
  26. Watanable, Y. & Imai, K. Analyt. Biochem. 116, 471–472 (1981).
    Article Google Scholar

Download references

Author information

Author notes

  1. Bruce P. Babbitt, Paul M. Allen and Emil R. Unanue: Washington University School of Medicine, St Louis, Missouri 63110, USA
  2. Gary Matsueda and Edgar Haber: Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA

Authors and Affiliations

  1. Department of Pathology, Harvard Medical School, Boston, Massachusetts, 02115, USA
    Bruce P. Babbitt, Paul M. Allen, Gary Matsueda, Edgar Haber & Emil R. Unanue

Authors

  1. Bruce P. Babbitt
    You can also search for this author inPubMed Google Scholar
  2. Paul M. Allen
    You can also search for this author inPubMed Google Scholar
  3. Gary Matsueda
    You can also search for this author inPubMed Google Scholar
  4. Edgar Haber
    You can also search for this author inPubMed Google Scholar
  5. Emil R. Unanue
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Babbitt, B., Allen, P., Matsueda, G. et al. Binding of immunogenic peptides to Ia histocompatibility molecules.Nature 317, 359–361 (1985). https://doi.org/10.1038/317359a0

Download citation