Developmental regulation of TCR efficiency

Unresponsiveness of mature T cells to the same self-peptide/self-MHC molecu le complexes with which thymocytes have reacted during positive selection r esults from an increase of activation thresholds during maturation. The mol ecular events accounting for this increase are still unknown. In mature cel ls, a strong correlation between the extent of TCR downmodulation and T cel l responses has been demonstrated. Exploiting this relationship, we show th at the efficiency with which the TCR mediates full signaling is development ally regulated. It decreases with thymic maturation and then increases with differentiation of naive T cells into memory lymphocytes. This analysis ba sed on TCR modulation revealed an unexpected characteristic of the T cell r eceptor: its ability to signal fully is regulated inversely by its level of expression. This latter relationship may apply to other receptors both wit hin and outside the immune system.