Structure of the Vdelta domain of a human gammadelta T-cell antigen receptor.
Structure of the Vdelta domain of a human gammadelta T-cell antigen receptor.
复制标题
人 γδ T 细胞抗原受体的 Vδ 结构域的结构。
作者：
H. Li;M. Lebedeva;A. Llera;B. A. Fields;M. Brenner;R. Mariuzza
T淋巴细胞的抗原识别由称为T细胞抗原受体（TCR）的细胞表面糖蛋白介导。它们由具有可变区（V）和恒定区（C）的α和β或γ和δ多肽链组成。与α TCR相比，α TCR仅识别与主要组织相容性复合体（MHC）分子结合的肽片段形式的抗原，γ δ TCR似乎直接识别蛋白质，而无需抗原加工，并且独立于结合的肽识别MHC分子。此外，小的含磷酸盐的非肽化合物也已被鉴定为某些γ δ T细胞的配体。这些研究表明，γ δ TCR的抗原识别可能与α TCR的抗原识别根本不同。已经确定了几种α TCR和TCR片段及其与肽-MHC或超抗原的复合物的三维结构。在这里，我们以1.9 A的分辨率报告了人类γ δ TCR的V δ结构域的晶体结构。与抗体和α TCR V结构域的比较揭示，V δ的框架结构与Vh的框架结构比Valpha、V β或Vl（其中H和L指重链和轻链）更接近，而其互补决定区（CDR）的相对位置和构象共享Valpha和Vh的特征。这些结果提供了γ δ TCR在结构上不同于α TCR的第一个直接证据，并且连同TCR δ链的CDR 3长度分布与免疫球蛋白重链的CDR 3长度分布相似的观察结果，与功能研究一致，表明γ δ TCR对某些抗原的识别可能类似于抗体对抗原的识别。
Antigen recognition by T lymphocytes is mediated by cell-surface glycoproteins known as T-cell antigen receptors (TCRs). These are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. In contrast to alphabeta TCRs, which recognize antigen only as peptide fragments bound to molecules of the major histocompatibility complex (MHC), gammadelta TCRs appear to recognize proteins directly, without antigen processing, and to recognize MHC molecules independently of the bound peptide. Moreover, small phosphate-containing non-peptide compounds have also been identified as ligands for certain gammadelta T cells. These studies indicate that antigen recognition by gammadelta TCRs may be fundamentally different from that by alphabeta TCRs. The three-dimensional structures of several alphabeta TCRs and TCR fragments, and their complexes with peptide-MHC or superantigens, have been determined. Here we report the crystal structure of the Vdelta domain of a human gammadelta TCR at 1.9 A resolution. A comparison with antibody and alphabeta TCR V domains reveals that the framework structure of Vdelta more closely resembles that of VH than of Valpha, Vbeta or VL (where H and L refer to heavy and light chains), whereas the relative positions and conformations of its complementarity-determining regions (CDRs) share features of both Valpha and VH. These results provide the first direct evidence that gammadelta TCRs are structurally distinct from alphabeta TCRs and, together with the observation that the CDR3 length distribution of TCR delta chains is similar to that of immunoglobulin heavy chains, are consistent with functional studies suggesting that recognition of certain antigens by gammadelta TCRs may resemble antigen recognition by antibodies.