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

• Published in: Nature (London) 1995-11, Vol.378 (6554), p.295-298
• Main Authors: Cao, Wuxiong, Tykodi, Scott S, Esser, Mark T, Braciale, Vivian L, Braciale, Thomas J
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Cell Death; Cell Line; Clone Cells; DNA; Fundamental and applied biological sciences. Psychology; Fundamental immunology; H-2 Antigens - immunology; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral - immunology; Humanities and Social Sciences; Immunobiology; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - immunology; letter; Leukocyte Common Antigens - immunology; Lymphocyte Activation; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Membrane Glycoproteins - immunology; Mice; Molecular Sequence Data; multidisciplinary; Myeloma Proteins - genetics; Myeloma Proteins - immunology; Peptide Fragments - immunology; Perforin; Pore Forming Cytotoxic Proteins; Receptors, Antigen, T-Cell - immunology; Science; Science (multidisciplinary); Signal Transduction
• ISSN: 0028-0836; 1476-4687
• 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 1–3 . CD8 + T cells may also be partially antagonized by such peptides 4,5 , and self-derived peptides of this type may play a role in CD8 + T cell selection in the thymus 6–8 . Activated CD8 + T cells lyse their targets by perforin-dependent granule exocytosis 9,10 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 K d -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 16 , 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.