Posttranslational regulation of TCR Vα allelic exclusion during T cell differentiation

We have previously shown that phenotypic allelic exclusion of TCR α- chain is functional only in mature thymocytes. A significant proportion of immature thymocytes (TCR(low)) express more than one cell surface α-chain, but mature thymocytes (TCR(high)) show phenotypic allelic exclusion and express only a single α-chain. We have analyzed thymocytes for both surface and intracellular α-chain expression and find that the majority of mature thymocytes express a second α-chain intracellularly. This result is predicted by a model in which the developmentally regulated allelic exclusion of the TCR α-chain is caused by competition between α-chains for the β- chain rather than by models in which one α-chain is down-regulated or in which selection favors cells with only a single α-chain species. Changes in the relative amounts of α- and β-chains available for pairing may therefore allow competition between the two α-chains for the β-chain. Peripheral T cells also frequently express second α-chains in the cytoplasm (18-27%), despite a rather low frequency of dual α-chain expression on the cell surface (2-4%). The frequency of nonsurface expressed α-chains is reduced somewhat compared with thymocytes, indicating that an additional level of control of allelic exclusion operates during the maturation of peripheral T cells.