RECEPTOR-SPECIFIC ALLELIC EXCLUSION OF TCRV-ALPHA-CHAINS DURING DEVELOPMENT

Expression of a single Ag receptor on lymphocytes is maintained via al lelic exclusion that generates cells with a clonal receptor repertoire . We show in normal mice and mice expressing functionally rearranged T CR alpha beta transgenes that allelic exclusion at the TCR alpha locus is not operational in immature thymocytes, whereas most mature T cell s express a single TCRV alpha-chain. TCRV alpha allelic exclusion in m ature thymocytes is regulated through a CD45 tyrosine phosphatase-medi ated signal during positive selection. Using functional and genetic sy stems for selection of immature double TCRV alpha(+) thymocytes, we sh ow that peptide-specific ligand recognition provides the signal for al lelic exclusion, i.e., mature T cells maintain expression of the ligan d-specific TCRV alpha-chain, but lose the nonfunctional receptor. Wher eas activation of TCRV beta-chains or CD3 epsilon leads to receptor in ternalization, TCRV alpha ligation promotes retention of the TCR on th e cell surface. Although both TCRV alpha- and TCRV beta-chains trigger phosphotyrosine signaling, only the TCRV beta-chain mediates membrane recruitment of the GTPase dynamin, These data indicate that TCRV alph a-directed signals for positive selection control allelic exclusion in T cells, and that developmental signals can select for single recepto r usage.