Kobayashi Yukihiro, Ikeda Kaori, Shiomi Kazuo
Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan.
Mol Biochem Parasitol. 2010 Dec;174(2):128-31. doi: 10.1016/j.molbiopara.2010.07.005. Epub 2010 Jul 22.
Ani s 1, the major allergen of Anisakis simplex, is expected to be a useful antigen in allergen-specific immunotherapy of Anisakis allergy. To avoid side-effects such as anaphylactic shock in immunotherapy, it is desirable to use not native allergens but hypoallergenic mutants devoid of IgE-binding epitopes. This study was hence aimed to elucidate IgE-binding epitopes of Ani s 1 toward the development of hypoallergenic Ani s 1 mutants. Mapping experiments using 32 peptides (P1-32) revealed that major IgE-binding epitopes are included in P24 (region 116-130) and P28 (region 136-150). Furthermore, Ala-scanning and truncation experiments established that eight (underlined in the sequence 116-ELFAREYEGVCKSGK-130) and nine amino acid residues (underlined in the sequence 136-RGSGWMMTILGKSCD-150) are crucial for the IgE-binding of P24 and P28, respectively. The determined crucial residues of P24 and P28 were assumed to be involved in electrostatic and hydrophobic interactions with IgE, respectively.
简单异尖线虫的主要变应原Ani s 1有望成为异尖线虫过敏变应原特异性免疫疗法中的一种有用抗原。为避免免疫疗法中出现诸如过敏性休克等副作用,理想的做法是使用非天然变应原,而是缺乏IgE结合表位的低变应原性突变体。因此,本研究旨在阐明Ani s 1的IgE结合表位,以开发低变应原性的Ani s 1突变体。使用32种肽(P1 - 32)进行的定位实验表明,主要的IgE结合表位包含在P24(116 - 130区域)和P28(136 - 150区域)中。此外,丙氨酸扫描和截短实验确定,分别有8个氨基酸残基(序列116 - ELFAREYEGVCKSGK - 130中带下划线部分)和9个氨基酸残基(序列136 - RGSGWMMTILGKSCD - 150中带下划线部分)对P24和P28与IgE的结合至关重要。P24和P28中确定的关键残基分别被认为参与了与IgE的静电和疏水相互作用。