Abstract
The majority of peripheral T lymphocytes bear cell-surface antigen receptors comprised of a disulphide-linked αβ dimer1. In an immune response, this receptor endows T cells with specificities for foreign antigenic protein fragments bound to cell surface glycoproteins encoded in the major histocompatibility complex (MHC)2–5. At a high frequency (>1%), the same population of T lymphocytes responds to allogeneic MHC glycoproteins6–8, or to differences at other genetic loci termed Mls8,9, in conjunction with MHC10. The αβ-antigen receptor has been implicated in alloreactivity11–13 and Mls reactivity14–18. In fact, many monoclonal T-cell lines recognize a foreign protein fragment bound to self-MHC molecules and, in addition, recognize allogeneic MHC glycoproteins19–21, an Mls-encoded determinant 22–24, or both25. For at least one T-cell clone, a monoclonal antibody directed against the αβ antigen receptor has been shown to block activation induced by either antigen-bound self-MHC or by allogeneic MHC26. However, it remains to be demonstrated directly that a single αβ receptor can mediate antigen specificity, alloreactivity and Mls reactivity, a prerequisite to understanding the structural basis of these high-frequency cross-reactivities. To address this issue we have performed transfers of receptor chain genes from a multiple-reactive T-cell clone into an unrelated host T lymphocyte. We now demonstrate definitively that the genes encoding a single αβ-receptor chain pair can transfer the recognition of self-MHC molecules complexed with fragments of antigen, allogeneic MHC molecules, and an Mls-encoded determinant (presumably in conjunction with MHC). In this case the transfer of antigen specificity and alloreactivity requires a specific αβ-receptor chain combination, whereas Mls reactivity can be transferred with the β-chain gene alone into a recipient expressing a randomly selected α-chain.
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References
Kronenberg, M., Sin, G., Hood, L. E. & Shastri, N. A. Rev. Immun. 4, 529–591 (1986).
Zinkernagel, R. M. & Doherty, P. C. J. exp. Med 141, 1427–1436 (1975).
Babbitt, B., Allen, P. M., Matsueda, G., Haber, E. & Unanue, E. Nature 317, 359–361 (1985).
Dembic, Z. et al. Nature 320, 232–238 (1986).
Buus, S., Sette, A., Colon, S. M., Miles, C. & Grey, H. M. Science 235, 1353–1358 (1987).
Lindahl, K. F. & Wilson, D. B. J. exp. Med. 145, 508–522 (1977).
MacDonald, H. R. et al. Immun. Rev. 51, 93–123 (1980).
Miller, R. A. & Stutman, O. J. Immun. 128, 2258–2264 (1982).
Lutz, C. T., Glasebrook, A. L. & Fitch, F. W. Eur. J. Immun. 11, 726–734 (1981).
Janeway, C. A. Jr & Katz, M. E. J. Immun. 134, 2057–2063 (1985).
Gabert, J. et al. Cell 50, 545–554 (1987).
Sorger, S. B., Hedrick, S. M., Fink, P. J., Bookman, M. A. & Matis, L. A. J. exp. Med. 165, 279–301 (1987).
Matis, L. A., Sorger, S. B., McElligott, D. L., Fink, P. J. & Hedrick, S. M. Cell 51, 59–69 (1987).
Kappler, J. W., Staerz, V., White, J. & Marrack, P.-C. Nature 332, 35–40 (1988).
MacDonald, H. R. et al. Nature 332, 40–45 (1988).
Abe, R., Nacchio, M. S., Fox, B. & Hodes, R. J. 335, 827–830 (1988).
Fry, A. M. & Matis, L. A. Nature 335, 830–832 (1988).
Pullen, A., Marrack, P. & Kappler, J. Nature 335, 796–801 (1988).
Janeway, C. A. Jr, Lerner, E. A., Conrad, P. J. & Jones, B. Behring Inst. Mitt. 70, 200–209 (1982).
Butz, E. et al. Immunogenetics 22, 189–192 (1985).
Ashwell, J. D., Chen, C. & Schwartz, R. H. J. Immun. 136, 389–395 (1986).
Braciale, V. L. & Braciale, T. J. J. Immun. 127, 859–862 (1981).
Katz, M. E. & Janeway, C. A. Jr J. Immun. 134, 2064–2070 (1985).
Lynch, D. H., Gress, R. E., Needleman, B. W., Rosenberg, S. A. & Hodes, R. J. J. Immun. 134, 2071–2078 (1985).
Webb, S., Okamoto, A. & Sprent, J. J. Immun. 141, 1828–1834 (1988).
Kaye, J. & Janeway, C. A. Jr J. exp med. 159, 1397–1412 (1984).
Fink, P. J., Matis, L. A., McElligott, D. L., Bookman, M. & Hedrick, S. M. Nature 321, 219–226 (1986).
Engel, I. & Hedrick, S. M. Cell 54, 473–484 (1988).
Samelson, L. E., Germain, R. N. & Schwartz, R. N. Proc. natn. Acad. Sci. U.S.A. 80, 6972–6976 (1983).
Festenstein, H., Bishop, C. & Taylor, B. A. Immunogenetics 5, 357–361 (1977).
Abe, R., Ryan, J. J. & Hodes, R. J. J. exp. Med. 165, 1113–1129 (1987).
Pfeifer, J. D., McKenzie, D. T., Swain, S. L. & Putton, R. W. J. exp. Med. 166, 1464–1470 (1987).
Gunning, P., Leavitt, J., Muscat, G., Ng, S.-Y. & Uedes, L. Proc. natn. Acad. Sci. U.S.A. 84, 4831–4835 (1987).
Sen, R. & Baltimore, D. Cell 46, 705–716 (1986).
Wang, A., La, S.-D. & Mark, D. Science 224, 1431–1433 (1984).
Stall, A. M. & Loken, M. R. J. Immun. 132, 787–795 (1984).
Malissen et al. Cell 55, 49–59 (1988).
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Kaye, J., Hedrick, S. Analysis of specificity for antigen, Mls, and allogeneic MHC by transfer of T-cell receptor α- and β-chain genes. Nature 336, 580–583 (1988). https://doi.org/10.1038/336580a0
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DOI: https://doi.org/10.1038/336580a0
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