PERIPHERAL SELECTION OF ANTIGEN RECEPTOR JUNCTIONAL FEATURES IN A MAJOR HUMAN-GAMMA-DELTA SUBSET
PERIPHERAL SELECTION OF ANTIGEN RECEPTOR JUNCTIONAL FEATURES IN A MAJOR HUMAN-GAMMA-DELTA SUBSET
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DOI：
10.1002/eji.1830230405
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发表时间：
1993-04-01
影响因子：
5.4
通讯作者：
BONNEVILLE, M
中科院分区：
文献类型：
--
作者：
DAVODEAU, F;PEYRAT, MA;BONNEVILLE, M
最近的研究表明存在具有结构相同的T细胞受体（TcR）的鼠γ δ T细胞亚群，这表明与α T细胞不同，一些γ δ T细胞专门识别有限数量的单态性抗原。然而，这个问题在人类中仍然是开放的，因为他们的外周γ δ T细胞的TcR结构多样性被证明是广泛的。在这里，我们已经详细分析了TcR链基因表达的人Vgamma 9 + Vdelta 2+外周血淋巴细胞（PBL），一个主要的外周γ δ T细胞亚群在成人和目前的证据，抗原驱动的外周选择TcR γ和δ连接基序之间的这些细胞。首先，它表明，Vgamma 9 + Vdelta 2+细胞表达V9 JPC 1 γ链的比例是PBL之间比胸腺衍生的克隆高得多，这表明优先使用这个J γ段是不是由于配对或组合的限制。第二，对来源于Vgamma 9 + Vdelta 2 + PBL克隆的V9 JPC 1 γ转录物的分析揭示了具有有限的“N "核苷酸添加和VJ修剪的独特V9 JP γ序列的高流行率，这不能通过酶或抗原非依赖性结构限制来解释。第三，由大多数V γ 9 + Vdelta 2 + PBL克隆表达的TcR δ链，尽管在氨基酸组成和长度上不同，但携带高度独特的连接基序，在来自V γ 9-Vdelta 2 + PBL或V γ 9 + Vdelta 2+胸腺细胞的V2 DJ δ序列中以低得多的频率发现。总之，这些结果表明，使用独特的V γ和V δ基因的细胞具有共同的γ和δ连接特征，表明V γ 9 + V δ 2+淋巴细胞的体内选择是由高度有限数量的标称配体介导的。
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.