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人类单克隆 IgE 抗体——过敏反应的重要里程碑。

Human Monoclonal IgE Antibodies-a Major Milestone in Allergy.

机构信息

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.

Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA.

出版信息

Curr Allergy Asthma Rep. 2023 Jan;23(1):53-65. doi: 10.1007/s11882-022-01055-w. Epub 2022 Dec 2.

Abstract

PURPOSE OF REVIEW

Bound to its high affinity receptor on mast cells and basophils, the IgE antibody molecule plays an integral role in the allergic reaction. Through interactions with the allergen, it provides the sensitivity and specificity parameters for cell activation and mediator release that produce allergic symptoms. Advancements in human hybridoma technologies allow for the generation and molecular definition of naturally occurring allergen-specific human IgE monoclonal antibodies.

RECENT FINDINGS

A high-resolution structure of dust mite allergen Der p 2 in complex with Fab of the human IgE mAb 2F10 was recently determined using X-ray crystallography. The structure reveals the fine molecular details of IgE 2F10 binding its 750 Å conformational epitope on Der p 2. This review provides an overview of this major milestone in allergy, the first atomic resolution structure of an authentic human IgE epitope. The molecular insights that IgE epitopes provide will allow for structure-based design approaches to the development of novel diagnostics, antibody therapeutics, and immunotherapies.

摘要

目的综述

IgE 抗体分子与其在肥大细胞和嗜碱性粒细胞上的高亲和力受体结合,在过敏反应中发挥重要作用。通过与过敏原的相互作用,它为细胞激活和介质释放提供了敏感性和特异性参数,从而产生过敏症状。人类杂交瘤技术的进步使得能够生成和分子定义天然存在的过敏原特异性人 IgE 单克隆抗体。

最新发现

最近使用 X 射线晶体学技术确定了尘螨过敏原 Der p 2 与人类 IgE mAb 2F10 的 Fab 复合物的高分辨率结构。该结构揭示了 IgE 2F10 与其在 Der p 2 上的 750Å构象表位结合的精细分子细节。该综述概述了过敏领域的这一重要里程碑,即第一个真实的人 IgE 表位的原子分辨率结构。IgE 表位提供的分子见解将允许基于结构的设计方法来开发新型诊断、抗体治疗和免疫疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8097/9831959/a58b6c6606a8/11882_2022_1055_Fig1_HTML.jpg

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