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 immunod ominant 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 repe rtoire. This limitation may be due to selective pressure induced by en dogenous homologous ligands responsible for both positive and negative selection in the thymus and partial activation in peripheral T cell r esponses. 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 antagoni ze M.58-66-reactive T cells, presumably by the formation of altered HL A-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. (C) American Society for Histocompatibility and Immu nogenetics, 1997.