Tenuous paths in unexplored territory: From T cell receptor signaling to effector gene expression during thymocyte selection

Abstract During the last step of αβ T cell development, thymocytes that have rearranged genes encoding TCR chains and express CD4 and CD8 coreceptors are selected on the basis of their TCR reactivity to escape programmed cell death and become mature CD4 or CD8 T cells. This process is triggered by intrathymic TCR signaling, that activates ‘sensor’ transcription factors ‘constitutively’ expressed in DP thymocytes. Eventually, TCR-signaled thymocytes evolve effector transcriptional circuits that control basal metabolism, migration, survival and initiation of lineage-specific gene expression. This review examines how components of the ‘sensing’ transcription apparatus responds to positive selection signals, and highlights important differences with mature T cell responses. In a second part, we evaluate current observations and hypotheses on the connections between sensing transcription factors and effector circuitries.