Allelic Exclusion of the TCR α-Chain Is an Active Process Requiring TCR-Mediated Signaling and c-Cbl

摘要: Phenotypic allelic exclusion at the TCRα locus is developmentally regulated in thymocytes. Many immature thymocytes express two cell surface α-chain species. Following positive selection, vast majority of mature and peripheral T cells display a single α-chain. A posttranslational mechanism occurring same time as selection TCR up-regulation leads to this phenotypic exclusion. Different models have been proposed explain regulation In study, we report that not by competition between distinct α-chains for β-chain, dueling model, nor limiting CD3 ζ-chain TCRhigh Our data instead favor selective retention model where signal through specifically maintaining expression selected while nonselected internalized. The use inhibitors specific Lck and/or other Src kinases indicates role these protein tyrosine signaling events leading down-regulation nonselectable Loss ubiquitin ligase/TCR adapter molecule c-Cbl, which important down-modulation negative regulator signaling, increased dual on double-positive Thus, only there an causing exclusion, but differential ubiquitination c-Cbl may be factor down-modulated.