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 gamma/delta+ and alpha/beta+ lineages.