Transcriptional control of thymocyte positive selection

Thymocyte development proceeds through multiple regulated checkpoints to ensure that the mature T-cell population is useful for recognition of self major histocompatibility complex (MHC) molecules, but not overtly autoreactive. Developing cells pass the positive selection checkpoint when the T-cell receptor (TCR) on immature thymocytes engages self peptide/MHC with low affinity. The resulting signal transduction initiates migration, survival, maturation, allelic exclusion, and lineage commitment. The changes in gene expression necessary for all of these cellular events are controlled by transcription factors responsive to signals in immature thymocytes. Recent progress has defined a small group of transcription factors that can be clearly linked to regulation of gene expression during positive selection.