TCRδ gene rearrangements revealed by fine structure of the recombination junction in mice

The standard products of V(D)J recombination of immunoglobulin and T cell receptor genes are two kinds of DNA junction, a coding joint and a signal joint. TCRdelta V-D and D-D signal joints in adult mouse thymocytes were sequenced following PCR amplification. We observed differential nucleotide insertions at the Vdelta-Ddelta signal joints, depending on the Vdelta and Ddelta gene usage in the developmental stage. Nucleotide insertions at the Vdelta-Ddelta1 signal joints were less frequent for the Vdelta4,5 genes preferentially utilized in adult thymocytes than for the Vdelta3,6 genes, infrequently rearranged to Ddelta1. In addition to standard signal joints, unexpectedly, novel nonstandard products, "replacement joints" of Ddelta1 substituted downstream by the recombination signal sequence of Vdelta were also found. However, no Ddelta2-associated replacement joints other than Vdelta5 were found. The other replacement joints of Ddelta1-Ddelta2 recombination were also observed. The mutation in TCRbeta gene affected the frequency of nucleotide insertions at the V8-D8 signal joints and inhibited the formation of replacement joint. Recombination mechanism generating the replacement joint and the possible role of TCRbeta in up-regulation of TCRdelta gene rearrangements are discussed.