Thymocyte selection: From signaling to epigenetic regulation

Abstract During thymocyte development at the double positive stage, thymocytes are subjected to a TCR quality check process termed “thymocyte selection.” TCRs with proper binding capabilities to MHC molecules (with self-peptide) are able to transduce cell survival signals and allow the continuing of development to single positive T cells. It has been known that TCRs in DP cells can transduce signals with higher efficiency than peripheral mature T cells, even though they share most of the signaling components. Recent studies have revealed some thymocyte-specific signaling modulators including Themis and Tespa1. The activation of TCR signaling during positive selection results in the activation of several key transcription factors and extensive gene expression change, which has been revealed by newly developed systemic transcriptome analysis tools, and could be used for the evaluation of positive selection process. The fate determination postpositive selection is also governed on the epigenetic level including both DNA methylation and histone modifications.