Mechanisms Controlling Termination of V-J Recombination at the TCRγ Locus: Implications for Allelic and Isotypic Exclusion of TCRγ Chains1

Analyses of Vγ-Jγ rearrangements producing the most commonly expressed TCRγ chains in over 200 γδ TCR+ thymocytes showed that assembly of TCRγ V-region genes display properties of allelic exclusion. Moreover, introduction of functionally rearranged TCRγ and δ transgenes results in a profound inhibition of endogenous TCRγ rearrangements in progenitor cells. The extent of TCRγ rearrangements in these cells is best explained by a model in which initiation of TCRγ rearrangements at both alleles is asymmetric, occurs at different frequencies depending on the V or J segments involved, and is terminated upon production of a functional γδ TCR. Approximately 10% of the cells studied contained two functional TCRγ chains involving different V and Jγ gene segments, thus defining a certain degree of isotypic inclusion. However, these cells are isotypically excluded at the level of cell surface expression possibly due to pairing restrictions between different TCRγ and δ chains.

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