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.