S. aureus IgG-binding proteins SpA and Sbi:: Host speciticity and mechanisms of immune complex formation
S. aureus IgG-binding proteins SpA and Sbi:: Host speciticity and mechanisms of immune complex formation
复制标题
DOI：
10.1016/j.molimm.2007.10.021
复制
发表时间：
2008-03-01
影响因子：
3.6
通讯作者：
van den Elsen, Jean M. H.
中科院分区：
文献类型：
--
作者：
Atkins, Karen L.;Burman, Julia D.;van den Elsen, Jean M. H.
逃避宿主免疫反应是金黄色葡萄球菌致病性的核心，细胞壁相关蛋白A（SpA）结合免疫球蛋白G Fc片段的能力促进了这种逃避，从而阻碍吞噬作用和经典途径补体固定。SpA还通过与Fab片段的重链可变部分相互作用而作为B细胞超抗原，并通过与人IgG形成大的不溶性免疫复合物来隔离免疫球蛋白。在此我们表明，不溶性免疫复合物的形成除了由Fc介导外，还由（V - H（3 +））Fab片段的结合所介导，并且SpA与IgG Fc片段形成可溶性复合物。我们将这些结果与第二种葡萄球菌免疫球蛋白结合蛋白Sbi的结果进行了比较，并注意到该蛋白与人IgG沉淀仅需要Fc片段。SpA和Sbi的免疫球蛋白结合结构域与Fc复合物的同源模型揭示了Sbi不依赖Fab形成不溶性复合物的分子基础。最后，我们比较了来自人类菌株的spa和sbi基因序列与感染一系列动物宿主的基因序列，以确定Sbi和SpA是否已获得对宿主IgG的特异性。我们注意到这些基因的IgG结合结构域内具有显著的序列保守性，这与缺乏宿主特异性是一致的。Sbi不依赖Fab结合IgG可能具有重要的临床意义。在免疫吸附疗法中使用SpA会导致严重的副作用，据认为是由FcγR识别和补体固定所介导。Sbi与不溶性免疫复合物的形成仅通过Fc结合发生，并且游离的Fc区域不太可能用于FcγR识别和补体固定。（c）2007爱思唯尔有限公司。保留所有权利。
The evasion of the host immune response is central to the pathogenicity of Staphylococcus aureus, and is facilitated by the ability of the cell wall-associated protein A (SpA) to bind immunoglobulin G Fc fragments, thereby impeding phacocytosis and classical pathway complement fixation. SpA also acts as a B-cell superantigen through interactions with the heavy-chain variable part of Fab fragments, and sequesters immunoglobulins by forming large insoluble immune complexes with human IgG. Here we show that the formation of insoluble immune complexes is mediated by the binding of(V-H(3+)) Fab fragments in addition to Fc, and that SpA forms soluble complexes with IgG Fc fragments. We compared these results with those for Sbi, a second staphylococcal immunoglobulin-binding protein, and note that this protein requires only the Fc fragment for precipitation with human IgG. Homology models of immunoglobulin-binding domains of SpA and Sbi in complex with Fc reveal the molecular basis of the Fab-independent formation of insoluble complexes by Sbi. Finally, we compared the sequences of the spa and sbi genes from human strains to those infecting a range of animal hosts to determine whether Sbi and SpA have acquired specificity for host IgG. We note remarkable sequence conservation within the IgG-binding domains of these genes, consistent with a lack of host specificity. The Fab-independent binding of IgG by Sbi could have significant clinical implications. The use of SpA in immunoadsorption therapy can cause severe side-effects, thought to be mediated by Fc gamma R recognition and complement fixation. The formation of insoluble immune complexes with Sbi occurs only via Fc binding and free Fc regions are unlikely to be available for Fc gamma R recognition and complement fixation. (c) 2007 Elsevier Ltd. All rights reserved.