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

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