A single peptide--MHC complex positively selects a diverse and specific CD8 T cell repertoire

Pathogen recognition by T cells is dependent on their exquisite specificity for self--major histocompatibility complex (MHC) molecules presenting a bound peptide. Although this specificity results from positive and negative selection of developing T cells in the thymus, the relative contribution of these two processes remains controversial To address the relation between the selecting peptide--MHC complex and the specificity of mature T cells, we generated transgenic mice that express a single peptide--MHC class I complex. We demonstrate that positive selection of CD8 T cells in these mice results in an MHC-specific repertoire. Although selection on a single complex is peptide promiscuous, mature T cells are highly peptide specific. Thus, positive selection imparts MHC and peptide specificity on the peripheral CD8 T cell repertoire. 10.1126/science.1177627