Regulation of the mature human T cell receptor γ repertoire by biased V-J gene rearrangement

Abstract

To delineate how gene rearrangement influences the expressed human γδT cell repertoire, we generated T cell receptor γ (TCRγ) V domain-specific cDNA libraries from the peripheral lymphocytes of eight donors and sequenced a total of 232 TCRγ gene transcripts. The libraries consisted of both inframe and out-of-frame rearranged TCRγ genes. The in-frame TCRγ gene transcripts were used to determine the diversity of functional T cells, whereas the out-of-frame transcripts, primarily derived from αβ T cells, were used to assess the frequencies of TCR Vγ-Jγ rearrangements in progenitor T lymphocytes. The results showed that both sets of transcripts exhibited strikingly restricted Vγ-Jγ combinations. Only 11 of 40 potential Vγ-Jγ rearrangements were common ( ≥; 3% of total). The pattern of gene usage in the functional and nonfunctional transcripts was similar and did not differ markedly among donors. The only exception was the predominance of V'79-JP in potentially functional transcripts from seven of eight individuals. These results show that Vγ-Jγ rearrangement is nonrandom and suggest that the diversity of TCRγ genes in the functional γδ T cell repertoire partly depends upon preferentially rearranged Vγ-Jγ gene combinations. However, the expansion of Vγb9/ Vδ2 T cells in adult peripheral blood can only be explained by antigenic selection of relatively rare Vγ9-JP recombinants.