TCR delta gene rearrangements revealed by fine structure of the recombination junction in mice.

Abstract

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. TCR delta V-D and D-D signal joints in adult mouse thymocytes were sequenced following PCR amplification. We observed differential nucleotide insertions at the V delta-D delta signal joints, depending on the V delta and D delta gene usage in the developmental stage. Nucleotide insertions at the V delta-D delta 1 signal joints were less frequent for the V delta 4, 5 genes preferentially utilized in adult thymocytes than for the V delta 3, 6 genes, infrequently rearranged to D delta 1. In addition to standard signal joints, unexpectedly, novel nonstandard products, "replacement joints" of D delta 1 substituted downstream by the recombination signal sequence of V delta were also found. However, no D delta 2-associated replacement joints other than V delta 5 were found. The other replacement joints of D delta 1-D delta 2 recombination were also observed. The mutation in TCR beta gene affected the frequency of nucleotide insertions at the V delta-D delta signal joints and inhibited the formation of replacement joint. Recombination mechanism generating the replacement joint and the possible role of TCR beta in up-regulation of TCR delta gene rearrangements are discussed.