Developmentally programmed rearrangement of T cell receptor Vγ genes is controlled by sequences immediately upstream of the Vγ genes

Distinct subsets of gamma delta T cells expressing different V gamma and V delta chains arise in ordered waves during thymic development. In the murine J gamma 1-C gamma 1 cluster, the V gamma 3 gene segment is utilized earliest in fetal thymic development, in progenitors of dendritic epidermal T cells (DECs). The V gamma 2 gene segment predominates in the late fetal stages and beyond, in cells destined for the secondary lymphoid organs. Using transgenic TCR gamma recombination substrates, we demonstrate that this restricted V gamma gene usage is determined by developmentally targeted gene rearrangement. We show that sequences immediately upstream of the V gamma 2 and V gamma 3 genes direct the rearrangement pattern in adult thymocytes. Thus, the choice of V gamma gene for recombination is coordinated with distinct differentiation programs in gamma delta subsets.