Enhanced Phagocytic Activity of HIV-Specific Antibodies Correlates with Natural Production of Immunoglobulins with Skewed Affinity for FcγR2a and FcγR2b
Enhanced Phagocytic Activity of HIV-Specific Antibodies Correlates with Natural Production of Immunoglobulins with Skewed Affinity for FcγR2a and FcγR2b
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DOI：
10.1128/jvi.03403-12
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发表时间：
2013-05-01
影响因子：
5.4
通讯作者：
Alter, Galit
中科院分区：
文献类型：
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作者：
Ackerman, Margaret E.;Dugast, Anne-Sophie;Alter, Galit
虽然开发能够诱导中和抗体的艾滋病毒疫苗仍然是一个优先事项，但数十年的研究证明这是一项艰巨的任务。然而，越来越多的证据表明，具有利用先天免疫能力的抗体可能会提供一些保护。虽然重要的研究集中在抗体在获取和控制中的细胞溶解特性，但对额外效应子功能的作用知之甚少。在这项研究中，我们研究了HIV免疫复合物的抗体依赖性吞噬作用，我们观察到感染受试者的抗体介导这一关键效应功能的能力存在显着差异。我们观察到抗体驱动吞噬作用的能力的定量差异和它们的Fc γ R使用概况的定性差异。我们证明，来自对照者和未治疗进展者的抗体在大量血浆和HIV特异性IgG中表现出增加的吞噬活性、改变的Fc结构域糖基化以及与Fc γ R2a和Fc γ R2b的偏斜相互作用。虽然增加的吞噬活性可能通过清除炎性免疫复合物直接影响免疫活化，但也可能的是，Fc受体使用模式可能通过在吞噬驱动内化病毒被动降解、释放免疫调节细胞因子和趋化因子或引发更有效的适应性免疫应答后调节下游信号来调节免疫应答。
While development of an HIV vaccine that can induce neutralizing antibodies remains a priority, decades of research have proven that this is a daunting task. However, accumulating evidence suggests that antibodies with the capacity to harness innate immunity may provide some protection. While significant research has focused on the cytolytic properties of antibodies in acquisition and control, less is known about the role of additional effector functions. In this study, we investigated antibody-dependent phagocytosis of HIV immune complexes, and we observed significant differences in the ability of antibodies from infected subjects to mediate this critical effector function. We observed both quantitative differences in the capacity of antibodies to drive phagocytosis and qualitative differences in their Fc gamma R usage profile. We demonstrate that antibodies from controllers and untreated progressors exhibit increased phagocytic activity, altered Fc domain glycosylation, and skewed interactions with Fc gamma R2a and Fc gamma R2b in both bulk plasma and HIV-specific IgG. While increased phagocytic activity may directly influence immune activation via clearance of inflammatory immune complexes, it is also plausible that Fc receptor usage patterns may regulate the immune response by modulating downstream signals following phagocytosis-driving passive degradation of internalized virus, release of immune modulating cytokines and chemokines, or priming of a more effective adaptive immune response.