DEVELOPMENTALLY PROGRAMMED REARRANGEMENT OF T-CELL RECEPTOR V-GAMMA GENES IS CONTROLLED BY SEQUENCES IMMEDIATELY UPSTREAM OF THE V-GAMMA GENES

Distinct subsets of gamma delta T cells expressing different V gamma a nd 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 dend ritic epidermal T cells (DECs). The V gamma 2 gene segment predominate s in the late fetal stages and beyond, in cells destined for the secon dary lymphoid organs. Using transgenic TCR gamma recombination substra tes, we demonstrate that this restricted V gamma gene usage is determi ned by developmentally targeted gene rearrangement. We show that seque nces immediately upstream of the V gamma 2 and V gamma 3 genes direct the rearrangement pattern in adult thymocytes. Thus, the choice of V g amma gene for recombination is coordinated with distinct differentiati on programs in gamma delta subsets.