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
Swain, S. L. Proc. natn. Acad. Sci. U.S.A. 78, 7101–7105 (1981).
Landegren, U. et al. J. exp. Med. 155, 1579–1584 (1982).
Norment A. M., Salter, R. D., Parham, P., Engelhard, V. H. & Littman, D. R. Nature 336, 79–81 (1988).
Parham, P. et al. Proc. natn. Acad. Sci. U.S.A. 85, 4005–4009 (1988).
Auffray, C. & Novotny, J. Hum. Immun. 15, 381–390 (1986).
Mazerolles, F. et al. Cell 55, 497–504 (1988).
Bjorkman, P. J. et al. Nature 329, 506–512 (1987).
Bjorkman, P. J. et al. Nature 329, 512–518 (1987).
Van Seventer, G. A., Van Lier, R. A. W., Spits, H., Ivanyi, P. & Melief, C. J. M. Eur. J. Immun. 16, 1363–1371 (1986).
Fleischer, B., Schrezenmeier, H. & Wagner, H. J. Immun. 136, 1625–1628 (1986).
Potter, T. A., Rajan, T. V., Dick, R. F. & Bluestone, J. A. Nature 337, 73–75 (1989).
Connolly, J. M., Potter, T. A., Wormstall, E.-M. & Hansen, T. H. J. exp. Med. 168, 325–341 (1988).
Davis, M. M. & Bjorkman, P. J. Nature 334, 395–402 (1988).
Ennis, P. D., Jackson, A. P. & Parham, P. J. Immun. 141, 642–651 (1988).
HLA in Asia-Oceania, 1986 (ed. Aizawa, M.) (Hokkaido Univ. Press, Japan) (1986).
Gaston, J. S. H., Rickinson, A. B. & Epstein, M. A. Cell Immun. 94, 231–242 (1985).
Wallace, L. E., Kennedy, L. J., Landon, C., Bodmer, J. G. & Rickinson, A. B. Tissue Antigens 27, 298–307 (1986).
Salter, R. D., Clayberger, C., Lomen, C. E., Krensky, A. M. & Parham, P. J. exp. Med. 166, 283–288 (1987).
Russo, C., Ng, A.-K., Pellegrino, M. A. & Ferrone, S. Immunegenetics 18, 23–35 (1983).
Simpson, P. A., Spudich, J. A. & Parham, P. J. Cell Biol. 99, 287–295 (1984).
Martin, P. J., Ledbetter, J. A., Clark, E. A., Beatty, P. G. & Hansen, J. A. J. Immun. 132, 759–765 (1984).
Charron, D. J. & McDevitt, H. O. J. exp. Med. 152, 18s–36s (1980).
Clayberger, C. et al. J. exp. Med. 162, 1709–1714 (1985).
Hogan, K. T. et al. J. exp. Med 168, 725–736 (1988).
Gotch, F., Rothbard, J., Howland, K., Townsend, A. & McMichael, A. Nature 326, 881–882 (1987).
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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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DOI: https://doi.org/10.1038/338345a0
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