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Partial activation of CD8+ T cells by a self-derived peptide

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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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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