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Polymorphism in the α3 domain of HLA-A molecules affects binding to CD8

Nature volume 338, pages 345–347 (1989)Cite this article

Abstract

CYTOTOXIC T lymphocytes (CTL) expressing the CD8 glycoprotein recognize peptide antigens presented by class I major histocompatibility complex (MHC) molecules1,2. This correlation and the absence of CD8 polymorphism led to the hypothesis that CD8 binds to a conserved site of class I MHC molecules. Using a cell–cell binding assay we previously demonstrated specific interaction between human class I MHC (HLA-A,B,C) molecules and CD8 (ref. 3). Subsequent analysis of the products of 17 HLA-A,B alleles revealed a natural polymorphism for CD8 binding in the human population. Two molecules, HLA-Aw68.l and HLA-Aw68.2, which do not bind CD8, have a valine residue at position 245 whereas all other HLA-A,B,C molecules have alanine. Site-directed mutagenesis shows that this single substitution in the α3 domain is responsible for the CD8 binding phenotype and also affects recognition by alloreactive and influenza-specific CTL. Our results indicate that CD8 binds to the α3 domain of class I MHC molecules.

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References

  1. Swain, S. L. Proc. natn. Acad. Sci. U.S.A. 78, 7101–7105 (1981).

    Article  ADS  CAS  Google Scholar 

  2. Landegren, U. et al. J. exp. Med. 155, 1579–1584 (1982).

    Article  CAS  PubMed  Google Scholar 

  3. Norment A. M., Salter, R. D., Parham, P., Engelhard, V. H. & Littman, D. R. Nature 336, 79–81 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Parham, P. et al. Proc. natn. Acad. Sci. U.S.A. 85, 4005–4009 (1988).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Mazerolles, F. et al. Cell 55, 497–504 (1988).

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  9. Van Seventer, G. A., Van Lier, R. A. W., Spits, H., Ivanyi, P. & Melief, C. J. M. Eur. J. Immun. 16, 1363–1371 (1986).

    Article  CAS  Google Scholar 

  10. Fleischer, B., Schrezenmeier, H. & Wagner, H. J. Immun. 136, 1625–1628 (1986).

    CAS  PubMed  Google Scholar 

  11. Potter, T. A., Rajan, T. V., Dick, R. F. & Bluestone, J. A. Nature 337, 73–75 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Connolly, J. M., Potter, T. A., Wormstall, E.-M. & Hansen, T. H. J. exp. Med. 168, 325–341 (1988).

    Article  CAS  PubMed  Google Scholar 

  13. Davis, M. M. & Bjorkman, P. J. Nature 334, 395–402 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Ennis, P. D., Jackson, A. P. & Parham, P. J. Immun. 141, 642–651 (1988).

    CAS  PubMed  Google Scholar 

  15. HLA in Asia-Oceania, 1986 (ed. Aizawa, M.) (Hokkaido Univ. Press, Japan) (1986).

  16. Gaston, J. S. H., Rickinson, A. B. & Epstein, M. A. Cell Immun. 94, 231–242 (1985).

    Article  CAS  Google Scholar 

  17. Wallace, L. E., Kennedy, L. J., Landon, C., Bodmer, J. G. & Rickinson, A. B. Tissue Antigens 27, 298–307 (1986).

    Article  CAS  PubMed  Google Scholar 

  18. Salter, R. D., Clayberger, C., Lomen, C. E., Krensky, A. M. & Parham, P. J. exp. Med. 166, 283–288 (1987).

    Article  CAS  PubMed  Google Scholar 

  19. Russo, C., Ng, A.-K., Pellegrino, M. A. & Ferrone, S. Immunegenetics 18, 23–35 (1983).

    Article  CAS  Google Scholar 

  20. Simpson, P. A., Spudich, J. A. & Parham, P. J. Cell Biol. 99, 287–295 (1984).

    Article  CAS  PubMed  Google Scholar 

  21. Martin, P. J., Ledbetter, J. A., Clark, E. A., Beatty, P. G. & Hansen, J. A. J. Immun. 132, 759–765 (1984).

    CAS  PubMed  Google Scholar 

  22. Charron, D. J. & McDevitt, H. O. J. exp. Med. 152, 18s–36s (1980).

    CAS  PubMed  Google Scholar 

  23. Clayberger, C. et al. J. exp. Med. 162, 1709–1714 (1985).

    Article  CAS  PubMed  Google Scholar 

  24. Hogan, K. T. et al. J. exp. Med 168, 725–736 (1988).

    Article  CAS  PubMed  Google Scholar 

  25. Gotch, F., Rothbard, J., Howland, K., Townsend, A. & McMichael, A. Nature 326, 881–882 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology, Stanford University, Stanford, California, 94305, USA

    Russell D. Salter, Benjamin P. Chen & Peter Parham

  2. Department of Pediatrics, Stanford University, Stanford, California, 94305, USA

    Carol Clayberger & Alan M. Krensky

  3. Department of Microbiology and Immunology, University of California at San Francisco, California, 94143, USA

    Anne M. Norment & Dan R. Littman

  4. Howard Hughes Medical Institute, University of California at San Francisco, California, 94143, USA

    Dan R. Littman

Authors
  1. Russell D. Salter
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  2. Anne M. Norment
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  3. Benjamin P. Chen
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  4. Carol Clayberger
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  5. Alan M. Krensky
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  6. Dan R. Littman
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  7. Peter Parham
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Salter, R., Norment, A., Chen, B. et al. Polymorphism in the α3 domain of HLA-A molecules affects binding to CD8. Nature 338, 345–347 (1989). https://doi.org/10.1038/338345a0

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