Allelic exclusion at the TCRβ locus

Assembly of TCRβ chain variable-region genes is regulated in the context of allelic exclusion. Differential epigenetic modifications of the two TCRβ alleles established early in embryonic development may be important for permitting allelic exclusion by ordering rearrangement of the two alleles in double-negative thymocytes. Expression of a TCRβ chain, as part of the pre-TCR complex, activates signaling pathways that enforce allelic exclusion in double-positive thymocytes. These signaling pathways, which utilize p56lck and SLP-76, may be distinct from those used to promote other processes initiated by pre-TCR expression. In double-positive thymocytes allelic exclusion is enforced, in part, by changes in Vβ gene segment accessibility promoted by cis-acting elements that may be distinct from those regulating accessibility of D/Jβ gene segments.