Abstract
T CELLS are normally activated when the peptide for which they are specific is presented to them in the context of the appropriate major histocompatibility complex (MHC) (class I and Class II for CD8+ and CD4+ T cells, respectively). An increasing body of evidence indicates that structural homologues of the immunogenic peptide can partially activate or antagonize CD4+ T cells1–3. CD8+ T cells may also be partially antagonized by such peptides4,5, and self-derived peptides of this type may play a role in CD8+ T cell selection in the thymus6–8. Activated CD8+ T cells lyse their targets by perforin-dependent granule exocytosis9,10 and by inducing apoptosis mediated by CD95 (also known as Fas or APO1) with its ligand (CD95L)11–15. Here we show that a clone of Kd-restricted CD8+ T cells specific for influenza haemagglutinin, which can also be activated in a crossreactive manner by a peptide derived from a myeloma tumour immunoglobulin heavy-chain variable region (IgVH) to kill by both routes16, kills only by the CD95-CD95L pathway when stimulated by the corresponding germline IgVH peptide. As this germline IgVH peptide differs from the tumour peptide only at a single position buried in the MHC-binding groove, this indicates that CD95–CD95L-mediated killing can be triggered independently of the perforin-mediated pathway, and can be selectively affected by changes in MHC conformation.
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References
Evavold, B. D. & Allen, P. M. Science 252, 1308–1310 (1991).
Evavold, B. D., Williams, S. G., Hsu, B. L., Buus, S. & Allen, P. M. J. Immun. 148, 347–353 (1992).
Sette, A. et al. A. Rev. Immun. 12, 413–431 (1994).
Jameson, S. C., Carbone, F. R. & Bevan, M. J. J. exp. Med. 177, 1541–1550 (1993).
Bertoletti, A. et al. Nature 369, 407–410 (1994).
Jameson, S. C., Hogquist, K. A. & Bevan, M. J. Nature 369, 750–752 (1994).
Spain, L. M., Jorgensen, J. L., Davis, M. M. & Berg, L. J. J. Immun. 152, 1709–1717 (1994).
Hogquist, K. A. et al. Cell 76, 17–27 (1994).
Henkart, P. A. A. Rev. Immun. 3, 31–58 (1985).
Kagi, D. et al. Nature 369, 31–37 (1994).
Ito, N. et al. Cell 66, 233–243 (1991).
Ogasawara, J. et al. Nature 364, 806–809 (1993).
Lowin, B., Hahne, M., Mattmann, C. & Tschopp, J. Nature 370, 650–652 (1994).
Stalder, T., Hahn, S. & Erb, P. J. Immun. 152, 1127–1133 (1994).
Kagi, D. et al. Science 265, 528–530 (1994).
Cao, W., Myers-Powell, B. A. & Braciale, T. J. J. exp. Med. 179, 195–202 (1994).
Bodmer, H. C. et al. Cell 52, 253–258 (1988).
Walsh, C. M., Glass, A. A., Chiu, V. & Clark, W. R. J. Immun. 153, 2506–2514 (1994).
Matzinger, P. J. Immun. Meth. 145, 185–192 (1991).
Rouvier, E., Luciani, M.-F. & Golstein, P. J. exp. Med. 177, 195–200 (1993).
Ostergaard, H. L., Kane, K. P., Mescher, M. F. & Clark, W. R. Nature 330, 71–72 (1987).
Suda, T., Takahashi, T., Golstein, P. & Nagata, S. Cell 75, 1169–1178 (1993).
Suda, T. & Nagata, S. J. exp. Med. 179, 873–879 (1994).
Rammensee, H. G., Falk, K. & Rotzschke, O. A. Rev. Immun. 11, 213–244 (1993).
Sherman, L. A. & Chattopadhyay, S. A. Rev. Immun. 11, 385–402 (1993).
Chattopadhyay, S., Theohabd, M., Biggs, J. & Sherman, L. A. J. exp. Med. 179, 213–219 (1993).
Henkart, P. A. Immunity 1, 343–346 (1994).
Crispe, I. N. Immunity 1, 347–349 (1994).
Singer, G. G. & Abbas, A. K. Immunity 1, 365–371 (1994).
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Cao, W., Tykodi, S., Esser, M. et al. Partial activation of CD8+ T cells by a self-derived peptide. Nature 378, 295–298 (1995). https://doi.org/10.1038/378295a0
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DOI: https://doi.org/10.1038/378295a0
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