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Epitopes with similar physicochemical properties contribute to cross reactivity between peanut and tree nuts.
Molecular immunology Pub Date : 2020-05-19 , DOI: 10.1016/j.molimm.2020.03.017
Jacqueline B Nesbit 1 , Catherine H Schein 2 , Benjamin A Braun 3 , Stephen A Y Gipson 1 , Hsiaopo Cheng 1 , Barry K Hurlburt 1 , Soheila J Maleki 1
Affiliation  

Many individuals with peanut (PN) allergy have severe reactions to tree nuts (TN) such as walnuts or cashews. Although allergenic proteins in TN and PN have overall low identity, they share discrete sequences similar in physicochemical properties (PCP) to known IgE epitopes. Here, PCP-consensus peptides (cp, 13 aa and 31 aa) were identified from an alignment of epitope rich regions of walnut vicilin, Jug r 2, leader sequence (J2LS) and cross-reactive epitopes in the 2S albumins of peanut and synthesized. A peptide similarity search in the Structural Database of Allergenic Proteins (SDAP) revealed a network of peptides similar (low property distance, PD) to the 13 aa cp (13cp) in many different plant allergens. Peptides similar to the 13cp in PN and TN allergens bound IgE from sera of patients allergic to PN and TN in peptide microarray analysis. The 13cp was used to produce a rabbit consensus peptide antibody (cpAB) that detected proteins containing repeats similar to the 13cp in western blots of various nut extracts, in which reactive proteins were identified by mass spectrometry. The cpAB bound more specifically to allergens and nut extracts containing multiple repeats similar to the 13 cp, such as almond (Pru du 6), peanut (Ara h 2) and walnut (Jug r 2). IgE binding to various nut extracts is inhibited by recombinant J2LS sequence and synthetic 31cp. Thus, several repeated sequences similar to the 13cp are bound by IgE. Multiple similar repeats in several allergens could account for reaction severity and clinically relevant cross-reactivity to PN and TN. These findings may help improve detection, diagnostic, and therapeutic tools.

中文翻译:


具有相似理化性质的表位有助于花生和坚果之间的交叉反应。



许多花生(PN)过敏的人对核桃或腰果等坚果(TN)有严重反应。尽管 TN 和 PN 中的过敏蛋白整体同一性较低,但它们具有与已知 IgE 表位在理化特性 (PCP) 上相似的离散序列。在此,通过核桃豌豆球蛋白、Jug r 2、前导序列 (J2LS) 和花生 2S 白蛋白中交叉反应表位的比对,鉴定出 PCP 共有肽(cp、13 个氨基酸和 31 个氨基酸),并合成。过敏蛋白结构数据库 (SDAP) 中的肽相似性搜索揭示了与许多不同植物过敏原中的 13 aa cp (13cp) 相似的肽网络(低属性距离,PD)。在肽微阵列分析中,与 PN 和 TN 过敏原中的 13cp 相似的肽与来自对 PN 和 TN 过敏的患者血清中的 IgE 结合。 13cp 用于生产兔共有肽抗体 (cpAB),该抗体可在各种坚果提取物的蛋白质印迹中检测到含有与 13cp 相似的重复序列的蛋白质,其中通过质谱法鉴定反应性蛋白质。 cpAB 更特异地与含有与 13 cp 类似的多个重复的过敏原和坚果提取物结合,例如杏仁 (Pru du 6)、花生 (Ara h 2) 和核桃 (Jug r 2)。重组 J2LS 序列和合成 31cp 可抑制 IgE 与各种坚果提取物的结合。因此,与 13cp 相似的几个重复序列被 IgE 结合。几种过敏原中的多个相似重复可以解释反应的严重程度以及与 PN 和 TN 的临床相关交叉反应。这些发现可能有助于改进检测、诊断和治疗工具。
更新日期:2020-05-19
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