ALLELIC EXCLUSION OF MOUSE T-CELL RECEPTOR-ALPHA CHAINS OCCURS AT THETIME OF THYMOCYTE TCR UP-REGULATION

We report a detailed analysis of TCR V alpha and V beta chain expressi on on immature versus mature thymocytes of normal, TCR beta-transgenic , and TCR alpha-hemizygous mice. Chain pairing between TCR V alpha and V beta chains is random on immature thymocytes, but individual chain pairs are selected in mature thymocytes. This indicates that V alpha-V beta chain pairing preferences are determined during thymic selection , and not as a result of structural constraints. Dual V alpha chain ex pression is found frequently on immature, but not mature thymocytes. I t is not found in TCR alpha-hemizygous mice, showing that cell surface expression of dual alpha chains is caused by lack of allelic exclusio n in immature thymocytes. Down-regulation of one of the alpha chains o ccurs concurrently with differentiation from TCR(lo), CD69(-) to TCR(h i), CD69(+) phenotype, suggesting that it is associated with positive selection of the functional TCR.