Specific Recognition of Thymic Self-Peptides Induces the Positive Selection of Cytotoxic T Lymphocytes

AbstractTo understand how thymic selection gives rise to T cells that are capable of major histocompatibility complex (MHC)–restricted recognition of antigen but are tolerant of self, we directly examined how peptide/MHC ligands expressed on thymic epithelial cells trigger the positive selection of immature thymocytes. We demonstrate that abundant self-peptides, purified from the H-2Db molecules of thymic epithelial cells, are specifically recognized during the positive selection of CD8+ T cells, implying that positive selection generates a repertoire of T cells that is weakly self-reactive. We also found that this recognition is somewhat cross-reactive, thereby providing an explanation for how the specific recognition of a limited repertoire of thymic self-peptides can select a diverse repertoire of T cells