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

Nature volume 378, pages 295298 (16 November 1995) | Download Citation

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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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Author information

Affiliations

  1. Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA

    • Wuxiong Cao
    • , Scott S. Tykodi
    • , Mark T. Esser
    • , Vivian L. Braciale
    •  & Thomas J. Braciale
  2. Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA

    • Wuxiong Cao
    • , Mark T. Esser
    • , Vivian L. Braciale
    •  & Thomas J. Braciale
  3. PathologyDepartments of, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA

    • Thomas J. Braciale
  4. Division of Biology and Biomedical Science, Immunology Program, Washington University School of Medicine, St Louis, Missouri 63110, USA

    • Scott S. Tykodi

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https://doi.org/10.1038/378295a0

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