Self-peptide ligands affect T cell recognition of the homologous influenza A matrix virus peptide M.58-66: modification of the HLA-A2.1/peptide complex structure and T cell antagonism.
The cytotoxic T lymphocyte (CTL) response directed against the immunodominant peptide M.58-66 from the matrix of influenza A virus presented by the HLA-A2.1 molecule is characterized by a restricted T cell repertoire. This limitation may be due to selective pressure induced by endogenous homologous ligands responsible for both positive and negative selection in the thymus and partial activation in peripheral T cell responses. We have used three self-protein-derived peptides homologous to M.58-66 to study their HLA-A2.1 binding capacity and recognition by M.58-66-specific HLA-A2.1-restricted CTLs. We show that they antagonize M.58-66-reactive T cells, presumably by the formation of altered HLA-A2.1 complex conformations. The results are discussed with reference to the role of endogenous ligands homologous to antigenic peptides in T cell repertoire selection, tolerance, and overall regulation of the immune response.
Hlavac
F
F
Laborataire d'Immunologie des Pathologies Infectieuses et Tumorales, INSERM U445, ICGM, Université René Descartes, Paris, France.
Choppin
J
J
Guillet
J G
JG
D001324:Autoantigens / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D008024:Ligands; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D010455:Peptides / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology* / Q000378:metabolism*
D001324:Autoantigens; D015789:HLA-A2 Antigen; D008024:Ligands; D010446:Peptide Fragments; D010455:Peptides; D014763:Viral Matrix Proteins; C098952:influenza virus membrane protein (58-66)