REGULATION OF THE MATURE HUMAN-T CELL RECEPTOR-GAMMA REPERTOIRE BY BIASED V-J GENE REARRANGEMENT

To delineate how gene rearrangement influences the expressed human gammadelta T cell repertoire, we generated T cell receptor gamma (TCRgamma) V domain-specific cDNA libraries from the peripheral lymphocytes of eight donors and sequenced a total of 232 TCRgamma gene transcripts. The libraries consisted of both in-frame and out-of-frame rearranged TCRgamma genes. The in-frame TCRgamma gene transcripts were used to determine the diversity of functional T cells, whereas the out-of-frame transcripts, primarily derived from alphabeta T cells, were used to assess the frequencies of TCR Vgamma-Jgamma rearrangements in progenitor T lymphocytes. The results showed that both sets of transcripts exhibited strikingly restricted Vgamma-Jgamma combinations. Only 11 of 40 potential Vgamma-Jgamma rearrangements were common (greater-than-or-equal-to 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 Vgamma9-JP in potentially functional transcripts from seven of eight individuals. These results show that Vgamma-Jgamma rearrangement is nonrandom and suggest that the diversity of TCRgamma genes in the functional gammadelta T cell repertoire partly depends upon preferentially rearranged Vgamma-Jgamma gene combinations. However, the expansion of Vgamma9/Vdelta2 T cells in adult peripheral blood can only be explained by antigenic selection of relatively rare Vgamma9-JP recombinants.