PERIPHERAL SELECTION OF ANTIGEN RECEPTOR JUNCTIONAL FEATURES IN A MAJOR HUMAN-GAMMA-DELTA SUBSET

Recent studies demonstrating the existence of murine gammadelta T cell subsets with structurally identical T cell receptors (TcR) suggest that unlike alphabeta T cells, some gammadelta T cells are specialized in the recognition of a limited number of monomorphic antigens. However, this question still remains open in humans, since the TcR structural diversity of their peripheral gammadelta T cells was shown to be extensive. Here we have analyzed in detail the TcR chain genes expressed by human Vgamma9+Vdelta2+ peripheral blood lymphocytes (PBL), a major peripheral gammadelta T cell subset in adults and present evidence for an antigen-driven peripheral selection of both TcR gamma and delta junctional motifs among these cells. First, it is shown that the proportion of Vgamma9+Vdelta2+ cells expressing the V9JPC1 gamma chain is much higher among PBL than among thymus-derived clones, indicating that preferential use of this Jgamma segment is not due to pairing or combinatorial constraints. Second, analysis of V9JPC1 gamma transcripts derived from Vgamma9+Vdelta2+ PBL clones revealed a high prevalence of a unique V9JP gamma sequence with limited ''N'' nucleotide additions and VJ trimming, which could not be accounted for by enzymatic or antigen-independent structural limitations. Third, the TcR delta chain expressed by most Vgamma9+Vdelta2+ PBL clones, though diverse in amino acid composition and length, carried a highly distinctive junctional motif, found at a much lower frequency among V2DJdelta sequences derived from Vgamma9-Vdelta2+ PBL or Vgamma9+Vdelta2+ thymocytes. Together, these results which demonstrate shared gamma and delta junctional features by cells using unique Vgamma and Vdelta genes, suggest that in vivo selection of Vgamma9+Vdelta2+ lymphocytes is mediated by a highly restricted number of nominal ligands.