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

Nature. 1995 Nov 16;378(6554):295-8. doi: 10.1038/378295a0.


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 cells. CD8+ T cells may also be partially antagonized by such peptides, and self-derived peptides of this type may play a role in CD8+ T cell selection in the thymus. Activated CD8+ T cells lyse their targets by perforin-dependent granule exocytosis and by inducing apoptosis mediated by CD95 (also known as Fas or APO1) with its ligand (CD95L). 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 routes, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Death
  • Cell Line
  • Clone Cells
  • DNA
  • H-2 Antigens / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral / immunology
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology*
  • Leukocyte Common Antigens / immunology
  • Lymphocyte Activation*
  • Membrane Glycoproteins / immunology
  • Mice
  • Molecular Sequence Data
  • Myeloma Proteins / genetics
  • Myeloma Proteins / immunology*
  • Peptide Fragments / immunology*
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction


  • H-2 Antigens
  • H-2K(K) antigen
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral
  • Immunoglobulin Heavy Chains
  • Membrane Glycoproteins
  • Myeloma Proteins
  • Peptide Fragments
  • Pore Forming Cytotoxic Proteins
  • Receptors, Antigen, T-Cell
  • Perforin
  • DNA
  • Leukocyte Common Antigens