Randall Centre for Cell and Molecular Biophysics and School of Basic and Medical Biosciences, King's College London, London, UK; email:
Almirall, Barcelona, Spain; email:
Annu Rev Immunol. 2023 Apr 26;41:255-275. doi: 10.1146/annurev-immunol-061020-053712. Epub 2023 Feb 3.
The evolution of IgE in mammals added an extra layer of immune protection at body surfaces to provide a rapid and local response against antigens from the environment. The IgE immune response employs potent expulsive and inflammatory forces against local antigen provocation, at the risk of damaging host tissues and causing allergic disease. Two well-known IgE receptors, the high-affinity FcεRI and low-affinity CD23, mediate the activities of IgE. Unlike other known antibody receptors, CD23 also regulates IgE expression, maintaining IgE homeostasis. This mechanism evolved by adapting the function of the complement receptor CD21. Recent insights into the dynamic character of IgE structure, its resultant capacity for allosteric modulation, and the potential for ligand-induced dissociation have revealed previously unappreciated mechanisms for regulation of IgE and IgE complexes. We describe recent research, highlighting structural studies of the IgE network of proteins to analyze the uniquely versatile activities of IgE and anti-IgE biologics.
在哺乳动物中,IgE 的进化为身体表面增加了一层额外的免疫保护,以提供针对环境抗原的快速和局部反应。IgE 免疫反应利用强大的驱逐和炎症力量对抗局部抗原刺激,冒着损害宿主组织和引起过敏疾病的风险。两种众所周知的 IgE 受体,高亲和力 FcεRI 和低亲和力 CD23,介导 IgE 的活性。与其他已知的抗体受体不同,CD23 还调节 IgE 的表达,维持 IgE 的动态平衡。这种机制是通过适应补体受体 CD21 的功能而进化的。最近对 IgE 结构的动态特性、变构调节的能力以及配体诱导解离的潜力的深入了解,揭示了以前未被重视的 IgE 和 IgE 复合物调节机制。我们描述了最近的研究,强调了 IgE 蛋白网络的结构研究,以分析 IgE 和抗 IgE 生物制剂的独特多功能活性。