Fields B A, Malchiodi E L, Li H, Ysern X, Stauffacher C V, Schlievert P M, Karjalainen K, Mariuzza R A
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA.
Nature. 1996 Nov 14;384(6605):188-92. doi: 10.1038/384188a0.
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, diabetes mellitus and multiple sclerosis. 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. 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, and (3) a TCR V(alpha) domain, 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.
超抗原（SAgs）是病毒或细菌蛋白，可作为强效T细胞刺激剂，并与多种人类疾病有关，包括中毒性休克综合征、糖尿病和多发性硬化症。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异常大比例的T细胞群体受到刺激。我们在此报告了与金黄色葡萄球菌肠毒素C2和C3（SEC2、SEC3）复合的TCRβ链的晶体结构。这些引起中毒性休克和食物中毒的肠毒素，以相同方式与TCRβ链结合。β链的互补决定区2（CDR2）以及程度较轻的CDR1和高变区4（HV4），结合在SAgs两个结构域之间的裂隙中。因此，SAg结合位点与TCR的肽/MHC结合位点之间存在相当大的重叠。根据（1）β链-SEC3复合体、（2）葡萄球菌肠毒素B（SEB）与MHC分子之间的复合体以及（3）TCR V（α）结构域的晶体结构构建的TCR-SAg-MHC复合体模型显示，SAg充当TCR和MHC之间的楔子，将抗原肽从TCR结合位点移开。通过这种方式，SAg能够规避特定肽/MHC复合体激活T细胞的正常机制。
