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. TCRδ V-D and D-D signal joints in adult mouse thymocytes were sequenced following PCR amplification. We observed differential nucleotide insertions at the Vδ-Dδ signal joints, depending on the Vδ and Dδ gene usage in the developmental stage. Nucleotide insertions at the Vδ-Dδ1 signal joints were less frequent for the Vδ4,5 genes preferentially utilized in adult thymocytes than for the Vδ3,6 genes, infrequently rearranged to Dδ1. In addition to standard signal joints, unexpectedly, novel nonstandard products, "replacement joints" of Dδ1 substituted downstream by the recombination signal sequence of Vδ were also found. However, no Dδ2-associated replacement joints other than Vδ5 were found. The other replacement joints of Dδ1-Dδ2 recombination were also observed. The mutation in TCRβ gene affected the frequency of nucleotide insertions at the Vδ-Dδ signal joints and inhibited the formation of replacement joint. Recombination mechanism generating the replacement joint and the possible role of TCRβ in up-regulation of TCRδ gene rearrangements are discussed.