Antigen Binding to Secretory Immunoglobulin A Results in Decreased Sensitivity to Intestinal Proteases and Increased Binding to Cellular Fc Receptors
Antigen Binding to Secretory Immunoglobulin A Results in Decreased Sensitivity to Intestinal Proteases and Increased Binding to Cellular Fc Receptors
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DOI：
10.1074/jbc.m109.059220
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发表时间：
2010-01-08
影响因子：
4.8
通讯作者：
Corthesy, Blaise
中科院分区：
文献类型：
--
作者：
Duc, Melanie;Johansen, Finn-Eirik;Corthesy, Blaise
在肠道分泌物中，分泌型免疫球蛋白A(SIgA)在识别和清除肠道病原体方面起着重要的哨兵和保护作用。除了作为第一道防线，SIgA和SIGA中心点抗原免疫复合体还选择性地通过Peyer‘s斑块运输到粘膜相关淋巴组织中的树突状细胞，有助于免疫监视和免疫调节。为了解释免疫复合体在面对分泌物中大量过剩的游离SIgA时的意外运输，我们假设SIgA在抗原结合时经历了结构修改。为了解决这个问题，我们将特定的聚合IgA和SIgA与不同大小和复杂程度的抗原(蛋白质毒素、病毒、细菌)相关联。与游离抗体比较，发现洗肠液中的蛋白水解酶对上述三种抗原的敏感性均有不同程度的提高。抗原结合进一步影响针对抗体重链和轻链的多克隆抗血清的免疫反应性，作为抗原大小的函数。与表达在早幼粒细胞和上皮细胞表面的细胞受体(FcαRI和聚合免疫球蛋白受体)的游离抗体相比，这些构象变化促进了基于SIgA的免疫复合物的结合。这些数据表明，SIgA对抗原的识别触发了结构变化，从而赋予了抗体增强的受体结合特性。这将免疫复合体识别为整合了结合抗原的存在的特定结构实体，并通过SIgA增加了已知的免疫排斥和粘液锚定功能。
In intestinal secretions, secretory IgA (SIgA) plays an important sentinel and protective role in the recognition and clearance of enteric pathogens. In addition to serving as a first line of defense, SIgA and SIgA center dot antigen immune complexes are selectively transported across Peyer's patches to underlying dendritic cells in the mucosa-associated lymphoid tissue, contributing to immune surveillance and immunomodulation. To explain the unexpected transport of immune complexes in face of the large excess of free SIgA in secretions, we postulated that SIgA experiences structural modifications upon antigen binding. To address this issue, we associated specific polymeric IgA and SIgA with antigens of various sizes and complexity (protein toxin, virus, bacterium). Compared with free antibody, we found modified sensitivity of the three antigens assayed after exposure to proteases from intestinal washes. Antigen binding further impacted on the immunoreactivity toward polyclonal antisera specific for the heavy and light chains of the antibody, as a function of the antigen size. These conformational changes promoted binding of the SIgA-based immune complex compared with the free antibody to cellular receptors (Fc alpha RI and polymeric immunoglobulin receptor) expressed on the surface of premyelocytic and epithelial cell lines. These data reveal that antigen recognition by SIgA triggers structural changes that confer to the antibody enhanced receptor binding properties. This identifies immune complexes as particular structural entities integrating the presence of bound antigens and adds to the known function of immune exclusion and mucus anchoring by SIgA.