Division of Genetics, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Immunoglobulin Research Laboratory, Department of Experimental Immunohematology, Sanquin Research, Amsterdam, the Netherlands.
Nat Immunol. 2023 Aug;24(8):1244-1255. doi: 10.1038/s41590-023-01544-8. Epub 2023 Jul 6.
Humoral immune responses are characterized by complex mixtures of polyclonal antibody species varying in their isotype, target epitope specificity and affinity. Posttranslational modifications occurring during antibody production in both the antibody variable and constant domain create further complexity and can modulate antigen specificity and antibody Fc-dependent effector functions, respectively. Finally, modifications of the antibody backbone after secretion may further impact antibody activity. An in-depth understanding of how these posttranslational modifications impact antibody function, especially in the context of individual antibody isotypes and subclasses, is only starting to emerge. Indeed, only a minute proportion of this natural variability in the humoral immune response is currently reflected in therapeutic antibody preparations. In this Review, we summarize recent insights into how IgG subclass and posttranslational modifications impact IgG activity and discuss how these insights may be used to optimize therapeutic antibody development.
体液免疫反应的特征是多克隆抗体种类的复杂混合物，这些抗体在同种型、靶表位特异性和亲和力方面各不相同。在抗体可变区和恒定区产生抗体的过程中发生的翻译后修饰进一步增加了复杂性，并可分别调节抗原特异性和抗体Fc依赖性效应功能。最后，抗体分泌后其骨架的修饰可能会进一步影响抗体活性。对于这些翻译后修饰如何影响抗体功能，尤其是在个体抗体同种型和亚类的背景下，人们才刚刚开始有深入的了解。事实上，目前治疗性抗体制剂中仅反映了体液免疫反应中这种自然变异性的极小一部分。在本综述中，我们总结了关于IgG亚类和翻译后修饰如何影响IgG活性的最新见解，并讨论了如何利用这些见解来优化治疗性抗体的开发。
