Key Points Rhesus FcγR2A allotypes differ in their interactions with different IgG subclasses. Rhesus FcγR3A allotypes show little variation in IgG subclass interactions. Human and macaque IgG1 but not IgG2–4 exhibit similar IgG–FcγR interactions. The rhesus macaque is an important animal model for AIDS and other infectious diseases. However, the investigation of Fc-mediated Ab responses in macaques is complicated by species-specific differences in FcγRs and IgG subclasses relative to humans. To assess the effects of these differences on FcγR–IgG interactions, reporter cell lines expressing common allotypes of human and rhesus macaque FcγR2A and FcγR3A were established. FcγR-mediated responses to B cells were measured in the presence of serial dilutions of anti-CD20 Abs with Fc domains corresponding to each of the four subclasses of human and rhesus IgG and with Fc variants of IgG1 that enhance binding to FcγR2A or FcγR3A. All of the FcγRs were functional and preferentially recognized either IgG1 or IgG2. Whereas allotypes of rhesus FcγR2A were identified with responses similar to variants of human FcγR2A with higher (H131) and lower (R131) affinity for IgG, all of the rhesus FcγR3A allotypes exhibited responses most similar to the higher affinity V158 variant of human FcγR3A. Unlike responses to human IgGs, there was little variation in FcγR-mediated responses to different subclasses of rhesus IgG. Phylogenetic comparisons suggest that this reflects limited sequence variation of macaque IgGs as a result of their relatively recent diversification from a common IGHG gene since humans and macaques last shared a common ancestor. These findings reveal species-specific differences in FcγR–IgG interactions with important implications for investigating Ab effector functions in macaques.

中文翻译：

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恒河猴 FcγR2A 和 FcγR3A 的常见同种异型与人和猕猴 IgG 亚类的功能相互作用

要点 恒河猴 FcγR2A 同种异型与不同 IgG 亚类的相互作用不同。恒河猴 FcγR3A 同种异型在 IgG 亚类相互作用中几乎没有变化。人和猕猴 IgG1 而非 IgG2-4 表现出相似的 IgG-FcγR 相互作用。恒河猴是艾滋病和其他传染病的重要动物模型。然而，由于 FcγR 和 IgG 亚类相对于人类的物种特异性差异，对猕猴 Fc 介导的 Ab 反应的研究变得复杂。为了评估这些差异对 FcγR-IgG 相互作用的影响，建立了表达人类和恒河猴 FcγR2A 和 FcγR3A 常见同种异型的报告细胞系。FcγR 介导的对 B 细胞的反应是在连续稀释的抗 CD20 抗体存在下测量的，其中 Fc 域对应于人和恒河猴 IgG 的四个亚类中的每一个亚类，以及 IgG1 的 Fc 变体，可增强与 FcγR2A 或 FcγR3A 的结合。所有 FcγR 都是有功能的，并且优先识别 IgG1 或 IgG2。尽管鉴定出恒河猴 FcγR2A 的同种异型响应与对 IgG 具有较高 (H131) 和较低 (R131) 亲和力的人 FcγR2A 变体的反应相似，但所有恒河猴 FcγR3A 同种异型都表现出与人 FcγR3A 的较高亲和力 V158 变体最相似的反应。与对人 IgG 的反应不同，FcγR 介导的对不同亚类恒河猴 IgG 的反应几乎没有变化。系统发育比较表明，这反映了猕猴 IgG 的序列变异有限，这是由于人类和猕猴最后共享一个共同祖先后，它们从一个常见的 IGHG 基因相对较新地多样化。这些发现揭示了 FcγR-IgG 相互作用的物种特异性差异，对研究猕猴的 Ab 效应子功能具有重要意义。