Stephen W. Tuffs, Karine Dufresne, Aanchal Rishi, Nicholas R. Walton, John K. McCormick
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引用次数: 0
Abstract
Bacterial T cell superantigens (SAgs) are a family of microbial exotoxins that function to activate large numbers of T cells simultaneously. SAgs activate T cells by direct binding and crosslinking of the lateral regions of MHC class II molecules on antigen-presenting cells with T cell receptors (TCRs) on T cells; these interactions alter the normal TCR–peptide–MHC class II architecture to activate T cells in a manner that is independent of the antigen specificity of the TCR. SAgs have well-recognized, central roles in human diseases such as toxic shock syndrome and scarlet fever through their quantitative effects on the T cell response; in addition, numerous other consequences of SAg-driven T cell activation are now being recognized, including direct roles in the pathogenesis of endocarditis, bloodstream infections, skin disease and pharyngitis. In this Review, we summarize the expanding family of bacterial SAgs and how these toxins can engage highly diverse adaptive immune receptors. We highlight recent findings regarding how SAg-driven manipulation of the adaptive immune response may operate in multiple human diseases, as well as contributing to the biology and life cycle of SAg-producing bacterial pathogens. This Review provides an updated assessment of the expanding family of T cell-activating bacterial superantigens, emphasizing potential roles of these toxins in various disease states as well as their contribution to the evolution of the bacterial pathogens Staphylococcus aureus and Streptococcus pyogenes.
细菌 T 细胞超抗原(SAgs)是微生物外毒素的一个家族,具有同时激活大量 T 细胞的功能。SAgs 通过抗原递呈细胞上 MHC II 类分子的横向区域与 T 细胞上的 T 细胞受体(TCR)直接结合和交联来激活 T 细胞;这些相互作用改变了正常的 TCR 肽-MHC II 类结构,从而以一种独立于 TCR 抗原特异性的方式激活 T 细胞。通过对 T 细胞反应的定量影响,SAgs 在中毒性休克综合症和猩红热等人类疾病中发挥着公认的核心作用;此外,SAg 驱动的 T 细胞活化还产生了许多其他后果,包括在心内膜炎、血流感染、皮肤病和咽炎的发病机制中发挥直接作用。在这篇综述中,我们总结了不断扩大的细菌 SAg 家族,以及这些毒素如何与高度多样化的适应性免疫受体发生作用。我们重点介绍了最近的研究发现,即由 SAg 驱动的适应性免疫反应是如何在多种人类疾病中发挥作用的,以及对产生 SAg 的细菌病原体的生物学和生命周期的影响。
期刊介绍:
Nature Reviews Immunology is a journal that provides comprehensive coverage of all areas of immunology, including fundamental mechanisms and applied aspects. It has two international standard serial numbers (ISSN): 1474-1733 for print and 1474-1741 for online. In addition to review articles, the journal also features recent developments and new primary papers in the field, as well as reflections on influential people, papers, and events in the development of immunology. The subjects covered by Nature Reviews Immunology include allergy and asthma, autoimmunity, antigen processing and presentation, apoptosis and cell death, chemokines and chemokine receptors, cytokines and cytokine receptors, development and function of cells of the immune system, haematopoiesis, infection and immunity, immunotherapy, innate immunity, mucosal immunology and the microbiota, regulation of the immune response, signalling in the immune system, transplantation, tumour immunology and immunotherapy, and vaccine development.