Peripheral selection of antigen receptor junctional features in a major human gamma delta subset.
Recent studies demonstrating the existence of murine gamma delta T cell subsets with structurally identical T cell receptors (TcR) suggest that unlike alpha beta T cells, some gamma delta 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 gamma delta T cells was shown to be extensive. Here we have analyzed in detail the TcR chain genes expressed by human V gamma 9+V delta 2+ peripheral blood lymphocytes (PBL), a major peripheral gamma delta 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 V gamma 9+V delta 2+ cells expressing the V9JPC1 gamma chain is much higher among PBL than among thymus-derived clones, indicating that preferential use of this J gamma segment is not due to pairing or combinatorial constraints. Second, analysis of V9JPC1 gamma transcripts derived from V gamma 9+V delta 2+ 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 V gamma 9+V delta 2+ PBL clones, though diverse in amino acid composition and length, carried a highly distinctive junctional motif, found at a much lower frequency among V2DJ delta sequences derived from V gamma 9-V delta 2+ PBL or V gamma 9+V delta 2+ thymocytes. Together, these results which demonstrate shared gamma and delta junctional features by cells using unique V gamma and V delta genes, suggest that in vivo selection of V gamma 9+V delta 2+ lymphocytes is mediated by a highly restricted number of nominal ligands.
INSERM U211, Institut de Biologie, Nantes, France.
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F
Davodeau
M A
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Peyrat
M M
MM
Hallet
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I
Houde
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Vie
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Bonneville
D000595:Amino Acid Sequence; D000941:Antigens / Q000276:immunology; D001483:Base Sequence; D002999:Clone Cells; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D008969:Molecular Sequence Data; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000941:Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta