Division of Structural Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Miyagi, Japan.
Int J Mol Sci. 2021 Nov 26;22(23):12776. doi: 10.3390/ijms222312776.
Immunoglobulin G (IgG) is currently the most studied immunoglobin class and is frequently used in antibody therapeutics in which its beneficial effector functions are exploited. IgG is composed of two heavy chains and two light chains, forming the basic antibody monomeric unit. In contrast, immunoglobulin A (IgA) and immunoglobulin M (IgM) are usually assembled into dimers or pentamers with the contribution of joining (J)-chains, which bind to the secretory component (SC) of the polymeric Ig receptor (pIgR) and are transported to the mucosal surface. IgA and IgM play a pivotal role in various immune responses, especially in mucosal immunity. Due to their structural complexity, 3D structural study of these molecules at atomic scale has been slow. With the emergence of cryo-EM and X-ray crystallographic techniques and the growing interest in the structure-function relationships of IgA and IgM, atomic-scale structural information on IgA-Fc and IgM-Fc has been accumulating. Here, we examine the 3D structures of IgA and IgM, including the J-chain and SC. Disulfide bridging and -glycosylation on these molecules are also summarized. With the increasing information of structure-function relationships, IgA- and IgM-based monoclonal antibodies will be an effective option in the therapeutic field.
免疫球蛋白 G（IgG）是目前研究最多的免疫球蛋白类别，经常被用于抗体治疗，利用其有益的效应功能。IgG 由两条重链和两条轻链组成，形成基本的抗体单体单元。相比之下，免疫球蛋白 A（IgA）和免疫球蛋白 M（IgM）通常通过连接（J）链组装成二聚体或五聚体，与多聚免疫球蛋白受体（pIgR）的分泌成分（SC）结合，并被转运到粘膜表面。IgA 和 IgM 在各种免疫反应中起着关键作用，特别是在粘膜免疫中。由于其结构复杂性，这些分子在原子尺度上的 3D 结构研究进展缓慢。随着冷冻电镜和 X 射线晶体学技术的出现以及对 IgA 和 IgM 的结构-功能关系的日益关注，IgA-Fc 和 IgM-Fc 的原子尺度结构信息不断积累。在这里，我们检查了 IgA 和 IgM 的 3D 结构，包括 J 链和 SC。这些分子上的二硫键桥接和 -糖基化也进行了总结。随着结构-功能关系信息的不断增加，基于 IgA 和 IgM 的单克隆抗体将成为治疗领域的有效选择。
