Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908, USA.
J Biol Chem. 2012 Mar 2;287(10):7388-98. doi: 10.1074/jbc.M111.311159. Epub 2011 Dec 30.
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.
屋尘螨产生强效过敏原 Der p 1 和 Der f 1，可引起过敏致敏和哮喘。Der p 1 和 Der f 1 是半胱氨酸蛋白酶，可引起 80%的螨过敏患者的 IgE 反应，并具有促炎特性。它们的抗原结构尚不清楚。在这里，我们展示了天然 Der p 1 和 Der f 1 与单克隆抗体 4C1 形成复合物的晶体结构，该抗体与两种过敏原上的独特交叉反应表位结合，与 IgE 识别有关。4C1 表位由几乎相同的氨基酸序列和接触残基形成。接触残基的突变会导致 mAb 4C1 结合丧失，并降低 IgE 抗体结合。这些暴露于表面的残基是可以用于开发重组过敏原疫苗的分子靶标。
