Molecular Determinants for Antibody Binding on Group 1 House Dust Mite Allergens
Molecular Determinants for Antibody Binding on Group 1 House Dust Mite Allergens
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DOI：
10.1074/jbc.m111.311159
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发表时间：
2012-03-02
影响因子：
4.8
通讯作者：
Chapman, Martin D.
中科院分区：
文献类型：
--
作者：
Chruszcz, Maksymilian;Pomes, Anna;Chapman, Martin D.
屋尘螨产生强效过敏原Der p 1和Der f 1，导致过敏性致敏和哮喘。Der p 1和Der f 1是半胱氨酸蛋白酶，在80%的螨过敏受试者中引起IgE应答，并具有促炎特性。其抗原结构尚不清楚。在这里，我们提出了晶体结构的天然Der p 1和Der f 1与单克隆抗体，4C1，它结合到一个独特的交叉反应表位上的过敏原与IgE识别。4C1表位由几乎相同的氨基酸序列和接触残基形成。接触残基的突变消除mAb 4C1结合并降低IgE抗体结合。这些表面暴露的残基是可用于开发重组变应原疫苗的分子靶标。
House dust mites produce potent allergens, Der p 1 and Der f 1, that cause allergic sensitization and asthma. Der p 1 and Der f 1 are cysteine proteases that elicit IgE responses in 80% of mite-allergic subjects and have proinflammatory properties. Their antigenic structure is unknown. Here, we present crystal structures of natural Der p 1 and Der f 1 in complex with a monoclonal antibody, 4C1, which binds to a unique cross-reactive epitope on both allergens associated with IgE recognition. The 4C1 epitope is formed by almost identical amino acid sequences and contact residues. Mutations of the contact residues abrogate mAb 4C1 binding and reduce IgE antibody binding. These surface-exposed residues are molecular targets that can be exploited for development of recombinant allergen vaccines.