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[治疗性抗体的铰链区:一段短序列的重要意义]

[The hinge region of therapeutic antibodies: major importance of a short sequence].

作者信息

Deveuve Quentin, Gouilleux-Gruart Valérie, Thibault Gilles, Lajoie Laurie

机构信息

Université de Tours, EA7501 GICC (Groupe Innovation et Ciblage Cellulaire), équipe FRAME (Fc Récepteurs, Anticorps et MicroEnvironnement), 37032 Tours, France.

Université de Tours, EA7501 GICC (Groupe Innovation et Ciblage Cellulaire), équipe FRAME (Fc Récepteurs, Anticorps et MicroEnvironnement), 37032 Tours, France - Service d'immunologie, CHRU de Tours, 37044 Tours, France.

出版信息

Med Sci (Paris). 2019 Dec;35(12):1098-1105. doi: 10.1051/medsci/2019218. Epub 2020 Jan 6.

Abstract

The hinge region is a short sequence of the heavy chains (H) of antibodies linking the Fab (Fragment antigen binding) region to the Fc (Fragment crystallisable) region. The functional properties of the four IgG subclasses partly result from the sequence differences of their hinge regions as some amino acids of the lower hinge region are located within or in the close vicinity of the C1q and FcγR binding sites on the IgG H chains. In addition, the hinge is susceptible to proteolytic cleavage by many proteases present in tumor and/or inflammatory microenvironment capable of affecting functional responses. Thus, an optimal format of the hinge region remains a major challenge for the development of new therapeutic antibodies.

摘要

铰链区是抗体重链(H)的一段短序列,它将Fab(抗原结合片段)区与Fc(可结晶片段)区连接起来。四种IgG亚类的功能特性部分源于其铰链区的序列差异,因为下铰链区的一些氨基酸位于IgG重链上C1q和FcγR结合位点内或其附近。此外,铰链区易受肿瘤和/或炎症微环境中存在的许多蛋白酶的蛋白水解切割影响,这些蛋白酶能够影响功能反应。因此,开发新型治疗性抗体时,铰链区的最佳形式仍然是一个重大挑战。

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