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

Abstract

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.