Crystal structure of a T-cell receptor beta-chain complexed with a superantigen
Crystal structure of a T-cell receptor beta-chain complexed with a superantigen
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DOI：
10.1038/384188a0
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发表时间：
1996-11-14
期刊：
影响因子：
64.8
通讯作者：
Mariuzza, RA
中科院分区：
文献类型：
--
作者：
Fields, BA;Malchiodi, EL;Mariuzza, RA
超抗原(SAG)是一种病毒或细菌蛋白，可作为强大的T细胞刺激剂，并与许多人类疾病有关，包括中毒性休克综合征(1，2)、糖尿病(3)和多发性硬化症(4)。SAGS与T细胞受体(TCR)和主要组织相容性复合体(MHC)蛋白的相互作用导致不成比例的大部分T细胞群体的刺激[2]。本文报道了一种与金黄色葡萄球菌肠毒素C2和C3(SEC2，SEC3)结合的TCRβ链的晶体结构。这些肠毒素会导致中毒性休克和食物中毒，它们以相同的方式与TCRβ链结合。β链的互补决定区2(CDR2)以及CDR1和高变区4(HV4)在较小程度上结合在SAG的两个结构域之间的裂隙中。因此，在SAG结合位点和TCR的肽/MHC结合位点之间有相当大的重叠。由(1)β链-SEC3复合体，(2)葡萄球菌肠毒素B(SEB)与MHC分子之间的复合体(5)，以及(3)TCR Vα结构域(6)的晶体结构构建的TCR-SAG-MHC复合体的模型表明，SAG在TCR和MHC之间起到楔子的作用，将抗原肽从TCR结合部位移位。通过这种方式，SAG能够通过特定的多肽/MHC复合体绕过T细胞激活的正常机制。
SUPERANTIGENS (SAgs) are viral or bacterial proteins that act as potent T-cell stimulants and have been implicated in a number of human diseases, including toxic shock syndrome(1,2), diabetes mellitus(3) and multiple sclerosis(4). The interaction of SAgs with the T-cell receptor (TCR) and major histocompatibility complex (MHC) proteins results in the stimulation of a disproportionately large fraction of the T-cell population(2). We report here the crystal structures of the beta-chain of a TCR complexed with the Staphylococcus aureus enterotoxins C2 and C3 (SEC2, SEC3). These enterotoxins, which cause both toxic shock and food poisoning, bind in an identical way to the TCR beta-chain. The complementarity-determining region 2 (CDR2) of the beta-chain and, to lesser extents, CDR1 and hypervariable region 4 (HV4), bind in a cleft between the two domains of the SAgs. Thus, there is considerable overlap between the SAg-binding site and the peptide/MHC-binding sites of the TCR. A model of a TCR-SAg-MHC complex constructed from the crystal structures of (1) the beta-chain-SEC3 complex, (2) a complex between staphylococcal enterotoxin B (SEB) and an MHC molecule(5), and (3) a TCR V alpha domain(6), reveals that the SAg acts as a wedge between the TCR and MHC to displace the antigenic peptide away from the TCR combining site. In this way, the SAg is able to circumvent the normal mechanism for T-cell activation by specific peptide/MHC complexes.