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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.
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