Petersson Karin, Pettersson Helen, Skartved Niels Jörgen, Walse Björn, Forsberg Göran
Active Biotech Research AB, Lund, Sweden.
J Immunol. 2003 Apr 15;170(8):4148-54. doi: 10.4049/jimmunol.170.8.4148.
Staphylococcal enterotoxin H (SEH) is a bacterial superantigen secreted by Staphylococcus aureus. Superantigens are presented on the MHC class II and activate large amounts of T cells by cross-linking APC and T cells. In this study, RT-PCR was used to show that SEH stimulates human T cells via the Valpha domain of TCR, in particular Valpha10 (TRAV27), while no TCR Vbeta-specific expansion was seen. This is in sharp contrast to all other studied bacterial superantigens, which are highly specific for TCR Vbeta. It was further confirmed by flow cytometry that SEH stimulation does not alter the levels of certain TCR Vbeta. In a functional assay addressing cross-reactivity, Vbeta binding superantigens were found to form one group, whereas SEH has different properties that fit well with Valpha reactivity. As SEH binds on top of MHC class II, an interaction between MHC and TCR upon SEH binding is not likely. This concludes that the specific expansion of TCR Valpha is not due to contacts between MHC and TCR, instead we suggest that SEH directly interacts with the TCR Valpha domain.
葡萄球菌肠毒素H(SEH)是由金黄色葡萄球菌分泌的一种细菌超抗原。超抗原呈递于MHC II类分子上,并通过交联抗原呈递细胞(APC)和T细胞来激活大量T细胞。在本研究中,采用逆转录聚合酶链反应(RT-PCR)表明,SEH通过T细胞受体(TCR)的Vα结构域刺激人T细胞,尤其是Vα10(TRAV27),而未观察到TCR Vβ特异性扩增。这与所有其他已研究的细菌超抗原形成鲜明对比,后者对TCR Vβ具有高度特异性。流式细胞术进一步证实,SEH刺激不会改变某些TCR Vβ的水平。在一项针对交叉反应性的功能试验中,发现Vβ结合超抗原形成一组,而SEH具有与Vα反应性非常匹配的不同特性。由于SEH结合在MHC II类分子之上,因此SEH结合时MHC与TCR之间不太可能发生相互作用。由此得出结论,TCR Vα的特异性扩增并非由于MHC与TCR之间的接触,相反,我们认为SEH直接与TCR Vα结构域相互作用。