过敏性疾病在全球呈迅速发展趋势，其中尘螨是我国最主要的过敏源之一。然而，尘螨过敏原Der p2是如何特异性识别IgE抗体，从而诱发过敏的机制尚不清楚。因此，在分子水平研究IgE-Der p2复合物的相互作用是阐明尘螨过敏及推动生物医药发展的关键。前期实验结果显示，结构质谱技术如氢氘交换质谱（HDX-MS）、非变性自上而下质谱（Native top-down MS）等可提供蛋白复合物相互作用区域、构象变化等结构信息，但针对抗原-抗体复合物体系的整合结构质谱技术仍有待进一步开发。本项目拟整合Native top-down MS、HDX-MS和交联质谱等技术，以IgE-Der p2复合物为研究对象，旨在阐明“二者结合区域”和“导致复合物亲和力差异的根本原因”的关键科学问题，探究IgE-Der p2复合物结构与功能之间的关系。本项目的顺利开展有助于阐明尘螨过敏的致敏机制，推动免疫治疗发展。

Allergic diseases have been developing rapidly in the world, and dust mite allergy is one of the most important allergic diseases in China. However, the mechanism that how Der p2 specifically recognize IgE antibody so that inducing allergic symptoms remains unclear. Thus, the key to elucidating the sensitization mechanism of dust mite allergy and promoting the development of biomedicine is probing interactions of IgE-Der p2 complex at the molecular level. Preliminary experimental results show that structural mass spectrometry techniques, such as hydrogen-deuterium exchange mass spectrometry (HDX-MS) and native top-down MS can provide structural information on binding region and conformational changes of protein complexes, whereas it remains to be developed to combine multiple structural mass spectrometry techniques for antigen-antibody complex systems. In this proposal, we will take Der p2 allergen and specific IgE antibody as examples, and develop the integrated structural mass spectrometry, such as native top-down mass spectrometry, HDX-MS, and cross-linking mass spectrometry, aiming at answering two key scientific questions, e.g., where is the binding regions between IgE antibody and Der p2 allergen? And what is the root cause to induce different affinities of IgE-Der p2 complexes? This project will give insight into the relationship between structure and function of IgE-Der p2 complex. Moreover, it will contribute to clarifying the sensitization mechanism of dust mite and promoting the development of immunotherapy.