Identification and sequence of a fourth human T cell antigen receptor chain
Identification and sequence of a fourth human T cell antigen receptor chain
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第四条人类 T 细胞抗原受体链的鉴定和序列
作者：
E. Loh;L. Lanier;C. Turck;D. Littman;Mark M. Davis;Y. Chien;A. Weiss
胸腺衍生的淋巴细胞（T细胞）利用克隆分布的抗原受体识别与主要组织相容性复合体（MHC）产物相关的肽片段（参考文献1-4）。在大多数鼠和人T细胞上，T细胞受体（TCR）由二硫键连接的α和β链（TCRα/β）组成，每个链均含有恒定和可变结构域，并与CD 3复合物的不变链相关5，6。然而，已经证明，在一小部分T细胞或未成熟胸腺细胞上表达不同的CD 3相关TCR，这些T细胞或未成熟胸腺细胞不能表达与II类或I类MHC抗原识别相关的分子CD 4或CD 8（参考文献7-14）。这些细胞表达γ和δ链的异二聚体（TRCγ/δ），而不是TCRα/β。编码α、β和γ的基因已被分离和表征15 -17。最近在小鼠J α C α基因座的5′端发现了一种新的小鼠T细胞受体（Cx）基因，该基因在T细胞个体发育早期经历重排和表达18。在这里，我们从PEER（一种表达TCRγ/δ的人类细胞系）中分离并测序了同源转录物，并显示其编码具有特征性V、D、J和C片段的蛋白质。使用来自该转录物的探针，我们已经表明，PEER和MOLT-13（另一种TCRγ/δ表达细胞系）都重排了该基因座，并表达了在3'非翻译区不同的两种大小的转录物。使用衍生自推断的C区序列的合成肽，我们制备了沉淀来自PEER和MOLT-13的TCR的δ链的抗血清，从而证明Cx及其人类同源物编码TCR的δ链。
Thymus-derived lymphocytes (T cells) use clonally distributed antigen receptors to recognize peptide fragments associated with products of the major histocompatibility complex (MHC) (refs 1–4). On most murine and human T cells the T cell receptor (TCR) is composed of disulphide-linked α and β chains (TCRα/β), each of which contains constant and variable domains, and which are associated with the invariant chains of the CD3 complex5,6. It has been demonstrated, however, that a distinct CD3-associated TCR is expressed on a small subset of T cells or immature thymocytes which fail to express either CD4 or CD8 (refs 7–14), the molecules associated with class II or class I MHC antigen recognition. Instead of TCRα/β, these cells express heterodimers of γ and δ chains (TRCγ/δ). The genes encoding α, β, and γ have been isolated and characterized15–17. A new murine T cell receptor (C x) gene which undergoes rearrangement and expression early during T cell ontogeny has recently been identified 5′ of the murine J α C α gene locus18. Here we isolate and sequence the homologous transcript from PEER, a human cell line that expresses a TCRγ/δ, and show that it encodes a protein with characteristic V, D, J, and C segments. Using probes derived from this transcript, we have shown that both PEER and MOLT-13, another TCRγ/δ-expressing cell line, rearrange this locus and express two sizes of transcripts differing in the 3' untranslated region. Using a synthetic peptide derived from the deduced C region sequence, we have prepared antisera that precipitates the δ chain of the TCR from both PEER and MOLT-13, thus demonstrating that C x and its human homologue code for the δ chain of the TCR.