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

Distinct subsets of gammadelta T cells expressing different Vgamma and Vdelta chains arise in ordered waves during thymic development. In the murine Jgamma1-Cgamma1 cluster, the Vgamma3 gene segment is utilized earliest in fetal thymic development, in progenitors of dendritic epidermal T cells (DECs). The Vgamma2 gene segment predominates in the late fetal stages and beyond, in cells destined for the secondary lymphoid organs. Using transgenic TCRgamma recombination substrates, we demonstrate that this restricted Vgamma gene usage is determined by developmentally targeted gene rearrangement. We show that sequences immediately upstream of the Vgamma2 and Vgamma3 genes direct the rearrangement pattern in adult thymocytes. Thus, the choice of Vgamma gene for recombination is coordinated with distinct differentiation programs in gammadelta subsets.