I型过敏反应的分子模型：一种非过敏性抗人IgE抗体片段的鉴定与表征，该片段可阻断IgE-FcεRI相互作用并与受体结合的IgE发生反应。

A molecular model of type I allergy: identification and characterization of a nonanaphylactic anti-human IgE antibody fragment that blocks the IgE-FcepsilonRI interaction and reacts with receptor-bound IgE.

作者信息

Laffer S, Hogbom E, Roux K H, Sperr W R, Valent P, Bankl H C, Vangelista L, Kricek F, Kraft D, Grönlund H, Valenta R

机构信息

Department of Pathophysiology, AKH, University of Vienna, Vienna, Austria.

出版信息

J Allergy Clin Immunol. 2001 Sep;108(3):409-16. doi: 10.1067/mai.2001.117593.

DOI:10.1067/mai.2001.117593

Abstract

BACKGROUND

The IgE-mediated activation of effector cells and antigen-presenting cells through the high-affinity receptor for IgE (FcepsilonRI) represents a key pathomechanism in type I allergy and many forms of asthma.

OBJECTIVE

We sought to establish an in vitro molecular model for the interaction of human FcepsilonRI, IgE, and the corresponding allergen and to identify monoclonal anti-human IgE antibodies with a therapeutic profile different from previously established anti-IgE antibodies.

METHODS

Human FcepsilonRI alpha chain, a human monoclonal allergen-specific IgE antibody (chimeric Bip 1), and the corresponding allergen, the major birch pollen allergen Bet v 1, were produced as recombinant proteins and analyzed by means of circular dichroism and native overlays, respectively. Using this molecular model, as well as negative stain immunoelectron microscopic analysis, and in vitro cultivated human basophils, we characterized mouse anti-human IgE antibodies.

RESULTS

We established a molecular model for the interaction of human IgE with FcepsilonRI. Using this molecular model, we identified a nonanaphylactic anti-human IgE antibody fragment (Fab12), which blocked the IgE-FcepsilonRI interaction and reacted with effector cell-bound IgE.

CONCLUSION

Fab12 represents a candidate molecule for therapy of atopy and asthma because it can be used for the depletion of circulating IgE antibodies, as well as for the depletion of IgE-bearing cells.

摘要

背景

通过IgE高亲和力受体（FcepsilonRI）介导的效应细胞和抗原呈递细胞的IgE激活是I型过敏和多种哮喘形式的关键发病机制。

目的

我们试图建立一个体外分子模型，用于研究人FcepsilonRI、IgE和相应变应原之间的相互作用，并鉴定具有不同于先前已建立的抗IgE抗体治疗特性的单克隆抗人IgE抗体。

方法

将人FcepsilonRIα链、人单克隆变应原特异性IgE抗体（嵌合Bip 1）和相应变应原——主要桦树花粉变应原Bet v 1作为重组蛋白进行表达，并分别通过圆二色性和天然蛋白印迹分析。利用该分子模型、负染免疫电子显微镜分析以及体外培养的人嗜碱性粒细胞，我们对小鼠抗人IgE抗体进行了表征。

结果

我们建立了人IgE与FcepsilonRI相互作用的分子模型。利用该分子模型，我们鉴定出一种非过敏性抗人IgE抗体片段（Fab12），它可阻断IgE-FcepsilonRI相互作用，并与效应细胞结合的IgE发生反应。

结论

Fab12是一种治疗特应性疾病和哮喘的候选分子，因为它可用于清除循环中的IgE抗体以及清除携带IgE的细胞。