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膜翅目毒液过敏中表位定位和分子靶向的潜力与局限性

Potential and limitations of epitope mapping and molecular targeting in Hymenoptera venom allergy.

作者信息

Fernandes Luís Gustavo Romani, Spillner Edzard, Jakob Thilo

机构信息

Experimental Dermatology and Allergy Research Group, Department of Dermatology and Allergology, University Medical Center Gießen-Marburg, Justus Liebig University Gießen, Gießen, Germany.

Laboratory of Translational Immunology, Internal Medicine Department, School of Medical Sciences, State University of Campinas, Campinas-SP, Brazil.

出版信息

Front Allergy. 2023 Dec 14;4:1327391. doi: 10.3389/falgy.2023.1327391. eCollection 2023.

Abstract

Hymenoptera venom (HV) allergy can lead to life threatening conditions by specific IgE (sIgE)-mediated anaphylactic reactions. The knowledge about major allergens from venom of different clinically relevant species increased in the last decades, allowing the development of component-resolved diagnostics in which sIgE to single allergens is analysed. Despite these advances, the precise regions of the allergens that bind to IgE are only known for few HV allergens. The detailed characterization of IgE epitopes may provide valuable information to improve immunodiagnostic tests and to develop new therapeutic strategies using allergen-derived peptides or other targeted approaches. Epitope-resolved analysis is challenging, since the identification of conformational epitopes present in many allergens demands complex technologies for molecular analyses. Furthermore, functional analysis of the epitopeś interaction with their respective ligands is needed to distinguish epitopes that can activate the allergic immune response, from those that are recognized by irrelevant antibodies or T cell receptors from non-effector cells. In this review, we focus on the use of mapping and molecular targeting approaches for characterization of the epitopes of the major venom allergens of clinically relevant Hymenoptera species. The screening of the most relevant allergen peptides by epitope mapping could be helpful for the development of molecules that target major and immunodominant epitopes blocking the allergen induced cellular reactions as novel approach for the treatment of HV allergy.

摘要

膜翅目毒液(HV)过敏可通过特异性IgE(sIgE)介导的过敏反应导致危及生命的状况。在过去几十年中,人们对不同临床相关物种毒液中的主要过敏原的了解有所增加,这使得能够开展组分分辨诊断,即分析针对单一过敏原的sIgE。尽管取得了这些进展,但只有少数几种HV过敏原与IgE结合的确切区域为人所知。对IgE表位进行详细表征可能会为改进免疫诊断测试以及利用过敏原衍生肽或其他靶向方法开发新的治疗策略提供有价值的信息。表位分辨分析具有挑战性,因为鉴定许多过敏原中存在的构象表位需要复杂的分子分析技术。此外,需要对表位与其各自配体的相互作用进行功能分析,以区分能够激活过敏免疫反应的表位与那些被无关抗体或来自非效应细胞的T细胞受体识别的表位。在这篇综述中,我们重点关注使用定位和分子靶向方法来表征临床相关膜翅目物种主要毒液过敏原的表位。通过表位定位筛选最相关的过敏原肽可能有助于开发靶向主要和免疫显性表位的分子,从而阻断过敏原诱导的细胞反应,这是治疗HV过敏的一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a08e/10755883/70da631e5e3b/falgy-04-1327391-g001.jpg

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