Structure and stability of 2S albumin-type peanut allergens:: implications for the severity of peanut allergic reactions
Structure and stability of 2S albumin-type peanut allergens:: implications for the severity of peanut allergic reactions
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DOI：
10.1042/bj20051728
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发表时间：
2006-05-01
影响因子：
4.1
通讯作者：
Rösch, P
中科院分区：
文献类型：
--
作者：
Lehmann, K;Schweimer, K;Rösch, P
对蛋白水解酶和热的抗性被认为是食物过敏原的先决条件。花生（Arachis hypogaea）中的过敏原是致命性食物过敏反应的最常见原因。在分子水平上研究了过敏原2S白蛋白Ara h 2和同源次要过敏原Ara h 6对天然和蛋白酶处理的过敏原的致敏效力。阿糖胞苷h 6的蛋白酶抗性核心的高分辨率溶液结构通过NMR光谱测定，并应用同源建模来生成阿糖胞苷h 2结构。阿糖胞苷h 2似乎是更有效的过敏原，即使这两种花生过敏原共享大量的交叉反应。这两种过敏原都含有对蛋白水解消化和高达100摄氏度的温度具有高度抵抗力的核心。尽管IgE抗体结合能力被蛋白酶处理降低，但从肥大细胞或嗜碱性粒细胞的功能等同物（人源化RBL（大鼠嗜碱性白血病）细胞）释放的介体证明IgE抗体结合能力的这种降低不一定转化为降低的过敏原效力。天然Ara h 2和Ara h 6与用消化酶处理的过敏原相比具有几乎相同的致敏效力。过敏原核心的折叠几乎彼此相同，并且与未消化蛋白质中相应区域的折叠相同。Ara It 2和Ara h 6的核心结构的极端免疫稳定性为即使在食品加工后过敏性效力的持续性提供了解释。
Resistance to proteolytic enzymes and heat is thought to be a prerequisite property of food allergens. Allergens from peanut (Arachis hypogaea) are the most frequent cause of fatal food allergic reactions. The allergenic 2S albumin Ara h 2 and the homologous minor allergen Ara h 6 were studied at the molecular level with regard to allergenic potency of native and protease-treated allergen. A high-resolution solution structure of the protease-resistant core of Ara h 6 was determined by NMR spectroscopy, and homology modelling was applied to generate an Ara h 2 structure. Ara h 2 appeared to be the more potent allergen, even though the two peanut allergens share substantial cross-reactivity. Both allergens contain cores that are highly resistant to proteolytic digestion and to temperatures of up to 100 degrees C. Even though IgE antibody-binding capacity was reduced by protease treatment, the mediator release from a functional equivalent of a mast cell or basophil, the humanized RBL (rat basophilic leukaemia) cell, demonstrated that this reduction in IgE antibody-binding capacity does not necessarily translate into reduced allergenic potency. Native Ara h 2 and Ara h 6 have virtually identical allergenic potency as compared with the allergens that were treated with digestive enzymes. The folds of the allergenic cores are virtually identical with each other and with the fold of the corresponding regions in the undigested proteins. The extreme immunological stability of the core structures of Ara It 2 and Ara h 6 provides an explanation for the persistence of the allergenic potency even after food processing.