Centre for Immunology, The Burnet Institute, Melbourne 3004, Australia.
J Biol Chem. 2011 Sep 23;286(38):33118-24. doi: 10.1074/jbc.M111.272252. Epub 2011 Jul 22.
Host survival depends on an effective immune system and pathogen survival on the effectiveness of immune evasion mechanisms. Staphylococcus aureus utilizes a number of molecules to modulate host immunity, including the SSL family of which SSL7 binds IgA and inhibits Fcα receptor I (FcαRI)-mediated function. Other Gram-positive bacterial pathogens produce IgA binding proteins, which, similar to SSL7, also bind the Fc at the CH2/CH3 interface (the junction between constant domains 2 and 3 of the heavy chain). The opposing activities of the host FcαRI-IgA receptor ligand pair and the pathogen decoy proteins select for host and pathogen variants, which exert stronger protection or evasion, respectively. Curiously, mouse but not rat IgA contains a putative N-linked glycosylation site in the center of this host receptor and pathogen-binding site. Here, we demonstrate that this site is glycosylated and that the effect of amino acid changes and glycosylation of the CH2/CH3 interface inhibits interaction with the pathogen IgA binding protein SSL7, while maintaining binding of pIgR, essential to the biosynthesis and transport of SIgA.
宿主的存活依赖于有效的免疫系统，而病原体的存活则依赖于其免疫逃避机制的有效性。金黄色葡萄球菌利用多种分子来调节宿主免疫，包括 SSL 家族，其中 SSL7 结合 IgA 并抑制 Fcα 受体 I（FcαRI）介导的功能。其他革兰氏阳性细菌病原体产生 IgA 结合蛋白，这些蛋白与 SSL7 类似，也结合重链的恒定结构域 2 和 3 之间的 CH2/CH3 界面（Fc）。宿主 FcαRI-IgA 受体配体对和病原体诱饵蛋白的相反作用选择了分别具有更强保护或逃避作用的宿主和病原体变体。奇怪的是，小鼠而不是大鼠 IgA 在这个宿主受体和病原体结合位点的中心含有一个假定的 N 连接糖基化位点。在这里，我们证明了该位点被糖基化，并且 CH2/CH3 界面的氨基酸变化和糖基化会抑制与病原体 IgA 结合蛋白 SSL7 的相互作用，同时保持与 pIgR 的结合，这对于 SIgA 的生物合成和转运至关重要。
