Developmentally Programmed Rearrangement of T Cell Receptor Vγ Genes Is Controlled by Sequences Immediately Upstream of the Vγ Genes

Abstract

Distinct subsets of γδ T cells expressing different Vγ and Vδ chains arise in ordered waves during thymic development. In the murine Jγ1–Cγ1 cluster, the Vγ3 gene segment is utilized earliest in fetal thymic development, in progenitors of dendritic epidermal T cells (DECs). The Vγ2 gene segment predominates in the late fetal stages and beyond, in cells destined for the secondary lymphoid organs. Using transgenic TCRγ recombination substrates, we demonstrate that this restricted Vγ gene usage is determined by developmentally targeted gene rearrangement. We show that sequences immediately upstream of the Vγ2 and Vγ3 genes direct the rearrangement pattern in adult thymocytes. Thus, the choice of Vγ gene for recombination is coordinated with distinct differentiation programs in γδ subsets.