Diversity of Vγ gene segments rearranged to the Jγ4 gene in mice

Because there are limited numbers of Vγ gene segments and most Vγ rearrangements occur within clusters of the Jγ-Cγ genes in mice, γ-chains display limited diversity compared with other TCR chains. In this study, we examined the nucleotide sequences of the Vγ-Jγ genes expressed in the γδ T cells appearing at the inflamed sites after Salmonella infection in DBA/2 mice. Most of the productive γ gene rearrangements were Vγ1-Jγ4, whereas Vγ2 and a unique Vγ, the 5' region of which was identical with sequences of the Vγ2 gene, and the 3' region of which was identical with that of the Vγ1 gene, were found to be rearranged to Jγ4 gene, albeit at low frequency. Analysis of the ontogenic appearance of the rearrangements in the Jγ4-Cγ4 locus revealed that Vγ2-Jγ4 gene rearrangement was frequent in fetal thymocytes at the early stage of gestation. Most of the early fetal Vγ2- Jγ4 rearrangements exhibited the identical junction, a nonfunctional canonical sequence. The sequence analysis of the coding joint and the reciprocal recombination signal joint suggests that short homology-mediated direct recombination and chromosomal inversion mechanism are involved in fetal Vγ2-Jγ4 gene rearrangement. Taken together, our data suggest that the recombination of multiple Vγ segments with Jγ4 can diversify the Vγ repertoire.