Mechanisms controlling termination of V-J recombination at the TCRγ locus:: Implications for allelic and isotypic exclusion of TCRγ chains

Analyses of V gamma-J gamma rearrangements producing the most commonly expressed TCR gamma chains in over 200 gamma delta TCR+ thymocytes; showed that assembly of TCR gamma V-region genes display properties of allelic exclusion. Moreover, introduction of functionally rearranged TCR gamma and delta transgenes results in a profound inhibition of endogenous TCR gamma rearrangements in progenitor cells. The extent of TCR gamma rearrangements in these cells is best explained by a model in which initiation of TCR gamma 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 gamma delta TCR. Approximately 10% of the cells studied contained two functional TCR gamma chains involving different V and J gamma 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 TCR gamma and 5 chains.