POSTTRANSLATIONAL REGULATION OF TCR V-ALPHA ALLELIC EXCLUSION DURING T-CELL DIFFERENTIATION

We have previously shown that phenotypic allelic exclusion of TCR alph a-chain is functional only in mature thymocytes. A significant proport ion of immature thymocytes (TCRlow) express more than one cell surface alpha-chain, but mature thymocytes (TCRhigh) show phenotypic allelic exclusion and express only a single alpha-chain, We have analyzed thym ocytes for both surface and intracellular alpha-chain expression and f ind that the majority of mature thymocytes express a second alpha-chai n intracellularly. This result is predicted by a model in which the de velopmentally regulated allelic exclusion of the TCR alpha-chain is ca used by competition between alpha-chains for the beta-chain rather tha n by models in which one alpha-chain is down-regulated or in which sel ection favors cells with only a single alpha-chain species, Changes in the relative amounts of alpha- and beta-chains available for pairing may therefore allow competition between the two alpha-chains for the b eta-chain. Peripheral T cells also frequently express second alpha-cha ins in the cytoplasm (18-27%), despite a rather low frequency of dual alpha-chain expression on the cell surface (2-4%). The frequency of no nsurface expressed alpha-chains is reduced somewhat compared with thym ocytes, indicating that an additional level of control of allelic excl usion operates during the maturation of peripheral T cells.