Reciprocal hybrid joints demonstrate successive V-J rearrangements on the same chromosome in the human TCR gamma locus

Novel variable (V)-joining (J) gene rearrangements are described in the human T cell receptor gamma locus, in which, on the one hand, the V3 variable gene is joined to the heptamer-nonamer recombination signals of the J1 segment and, on the other hand, the J1 segment is joined to the V3 recombination signals through head-to-head fusion. These recombination products, or hybrid joints, have been originated through an inversion of 47 kb DNA. Interestingly the inverted DNA stretch contains a normal V9-JP rearrangement. These findings are the first direct demonstration that successive rearrangements occur, on the same chromosome, in the human T cell receptor gamma locus, and suggest that the chronology of the joining events plays a role in the ontogeny of T cells and their differentiation in γ/δ+ and α/β+ lineages.