REARRANGEMENT AND DIVERSITY OF T-CELL RECEPTOR BETA-CHAIN GENES IN THYMOCYTES - A CRITICAL ROLE FOR THE BETA-CHAIN IN DEVELOPMENT

Thymocytes from mice congenitally deficient for TCR alpha chain synthesis were examined for the status of their TCR beta chain genes, by DNA sequencing and by a novel technique that analyzes populations of gene rearrangements. TCR beta chain genes were predominantly productively rearranged, in contrast with the statistical prediction for a quasi-random rearrangement process. Therefore, productive TCR beta chain gene rearrangement appears to be a critical step in thymocyte maturation, independent of TCR alpha chain expression. Moreover, the beta chain gene rearrangements in TCRalpha-/- mice are typical of those found in the thymus and periphery of normal mice. Thus, the extent of junctional diversity is a property of TCR genes that is imposed prior to selection on the mature alphabeta TCR.