An experimental and modeling-based approach to locate IgE epitopes of plant profilin allergens
An experimental and modeling-based approach to locate IgE epitopes of plant profilin allergens
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DOI：
10.1016/j.jaci.2007.02.004
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发表时间：
2007-06-01
影响因子：
14.2
通讯作者：
Pacios, Luis F.
中科院分区：
文献类型：
--
作者：
Lopez-Torrejon, Gema;Diaz-Perales, Araceli;Pacios, Luis F.
背景资料：植物profilins是肌动蛋白结合蛋白，形成了一个众所周知的泛过敏原家族，负责植物食物和花粉之间的交叉致敏。目的：研究瓜类过敏原蛋白Cue m 2三维结构上的IgE抗原决定簇。方法：应用瓜类过敏原特异性IgE水平较高的10例瓜类过敏患者的血清和混合血清，分析了瓜类过敏原蛋白Cue m 2三维结构上的IgE抗原决定簇。三维建模和潜在的表位定位是基于对Cue m 2表面的溶剂暴露和静电性质的分析。合成肽中具有最强IgE结合能力的残基定义了2个主要表位（E1，由残基66-75和81-93组成，和E2，由残基95-99和122-131组成），其与Cue m 2的肌动蛋白结合位点部分重叠。两个额外的表位（E3，包括残基2-10，和E4，包括残基35-45），应该显示较弱的推定抗原-抗体缔合，并且与具有低IgE结合能力的合成肽共享大部分残基。位于甜瓜profilin的三维结构中的不同类型的IgE表位可以构成解释该泛过敏原家族所表现出的致敏性和交叉反应性的分子基础。
Background: Plant profilins are actin-binding proteins that form a well-known panallergen family responsible for cross-sensitization between plant foods and pollens. Melon profilin, Cue m 2, is the major allergen of this fruit.Objective: We sought to map IgE epitopes on the 3-dimensional structure of Cue m 2.Methods: IgE binding to synthetic peptides spanning the full Cue m 2 amino acid sequence was assayed by using a serum pool and individual sera from 10 patients with melon allergy with significant specific IgE levels to this allergen. Three-dimensional modeling and potential epitope location were based on analysis of both solvent exposure and electrostatic properties of the Cue m 2 surface.Results: Residues included in synthetic peptides that exerted the strongest IgE-binding capacity defined 2 major epitopes (El, consisting of residues 66-75 and 81-93, and E2, consisting of residues 95-99 and 122-131) that partially overlapped with the actin-binding site of Cue m 2. Two additional epitopes (E3, including residues 2-10, and E4, including residues 35-45) that should show weaker putative antigen-antibody associations and shared most residues with synthetic peptides with low lgE-binding capacity were predicted on theoretical grounds.Conclusions: Strong and weak IgE epitopes have been uncovered in melon profilin, Cue m 2.Clinical implications: The different types of IgE epitopes located in the 3-dimensional structure of melon profilin can constitute the molecular basis to explain the sensitization and cross-reactivity exhibited by this panallergen family.