Dynamic tuning of T cell reactivity by self-peptide-major histocompatibility complex ligands

Intrathymic self-peptide-major histocompatibility complex class II (MHC) molecules shape the T cell repertoire through positive and negative selection of immature CD4(+)CCD8(+) thymocytes. By analyzing the development MCH class II-restricted T cell receptor (TCR) transgenic T cells under conditions in which the endogenous peptide repertoire is altered, we show: that self-peptide-MHC complexes are also involved in setting T cell activation thresholds. This occurs through changes ill the expression level of molecules on thymocytes that influence the sensitivity of TCR signaling. Our results suggest that the endogenous peptide repertoire modulates T cell responsiveness in the thymus in order to enforce tolerance to self-antigens.