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[从抗体对过敏原的识别到新的治疗概念]

[From the allergen-recognition by antibodies to new therapeutic concepts].

作者信息

Hantusch Brigitte, Jensen-Jarolim Erika

机构信息

Center für Physiologie und Pathophysiologie der Medizinischen Universität Wien, Währinger Gürtel 18-20, Vienna, Austria.

出版信息

Wien Med Wochenschr. 2008;158(1-2):13-8. doi: 10.1007/s10354-007-0496-5.

Abstract

Cross-linking of IgE antibodies through allergens is a basic event in type I allergy and leads to the immediate release of mediators like histamine, responsible for allergic symptoms like rhino-conjunctivitis or asthma. Critical for the binding of allergens to IgE are the IgE-epitopes, which represent a congregation of several amino acid residues often derived from different regions of the allergen. By means of the mimotope-technology, we isolated peptides from phage libraries, which were able to structurally mimic IgE-epitopes of the plant allergens Bet v 1 (birch) and Phl p 5a (timothy grass). Hence, these are candidates for an epitope-specific immunotherapy. In this mode of immunotherapy, it is the aim to induce IgG antibodies directed exclusively against the IgE-epitopes of allergens without induction of anaphylactogenic IgG species, and without the risk of anaphylaxis through cross-linking of IgE. Immunizing mice, we applied the mimotopes displayed on bacteriophages as well as on alternative carrier systems to enhance their antigenicity. With these systems it was possible to elicit an allergen-specific immune response, which was also accompanied by the appropriate T-cell help. Mimotopes resemble a promising concept for an epitope-tailored immunotherapy of allergic patients.

摘要

通过过敏原使IgE抗体交联是I型过敏反应的基本事件,并导致组胺等介质的立即释放,这些介质会引发如鼻结膜炎或哮喘等过敏症状。对于过敏原与IgE的结合至关重要的是IgE表位,它是由通常来自过敏原不同区域的几个氨基酸残基组成的集合。借助模拟表位技术,我们从噬菌体文库中分离出了能够在结构上模拟植物过敏原Bet v 1(桦树)和Phl p 5a(梯牧草)的IgE表位的肽。因此,这些肽是表位特异性免疫疗法的候选物。在这种免疫疗法模式中,目标是诱导仅针对过敏原IgE表位的IgG抗体,而不诱导具有过敏反应性的IgG种类,并且没有通过IgE交联引发过敏反应的风险。在免疫小鼠时,我们应用了展示在噬菌体以及替代载体系统上的模拟表位以增强其抗原性。利用这些系统有可能引发过敏原特异性免疫反应,同时还伴有适当的T细胞辅助。模拟表位对于针对过敏患者的表位定制免疫疗法而言是一个有前景的概念。

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