Diversity of V gamma gene segments rearranged to the J gamma 4 gene in mice.

Abstract

Because there are limited numbers of V gamma gene segments and most V gamma rearrangements occur within clusters of the J gamma-C gamma genes in mice, gamma-chains display limited diversity compared with other TCR chains. In this study, we examined the nucleotide sequences of the V gamma-J gamma genes expressed in the gamma delta T cells appearing at the inflamed sites after Salmonella infection in DBA/2 mice. Most of the productive gamma gene rearrangements were V gamma 1-J gamma 4, whereas V gamma 2 and a unique V gamma, the 5' region of which was identical with sequences of the V gamma 2 gene, and the 3' region of which was identical with that of the V gamma 1 gene, were found to be rearranged to J gamma 4 gene, albeit at low frequency. Analysis of the ontogenic appearance of the rearrangements in the J gamma 4-C gamma 4 locus revealed that V gamma 2-J gamma 4 gene rearrangement was frequent in fetal thymocytes at the early stage of gestation. Most of the early fetal V gamma 2-J gamma 4 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 V gamma 2-J gamma 4 gene rearrangement. Taken together, our data suggest that the recombination of multiple V gamma segments with J gamma 4 can diversify the V gamma repertoire.