表位
免疫球蛋白E
嗜碱性粒细胞活化
嗜碱性粒细胞
低过敏性
豚草
免疫学
艾蒿
过敏原
构象表位
过敏
表位定位
抗原性
分子模拟
抗体
化学
医学
替代医学
病理
作者
Maja Zabel,Milena Weber,Bernhard Kratzer,Cordula Köhler,Beatrice Jahn-Schmid,Gabriele Gadermaier,Pia Gattinger,Urška Bidovec-Stojkovič,Peter Korošec,Ursula Smole,Gert Wurzinger,Kuan-Wei Chen,Carmen Bunu Panaitescu,Ludger Klimek,Isabel Pablos,Katarzyna Niespodziana,Alina Neunkirchner,Walter Keller,Rudolf Valenta,Winfried F Pickl
标识
DOI:10.1016/j.jaci.2022.04.031
摘要
Background
Worldwide, pollen of the weed mugwort (Artemisia vulgaris) is a major cause of severe respiratory allergy, with its major allergen, Art v 1, being the key pathogenic molecule for millions of patients. Humanized mice transgenic for a human T-cell receptor specific for the major Art v 1 T-cell epitope and the corresponding HLA have been made. Objective
We sought to characterize IgE epitopes of Art v 1–sensitized patients and humanized mice for molecular immunotherapy of mugwort allergy. Methods
Four overlapping peptides incorporating surface-exposed amino acids representing the full-length Art v 1 sequence were synthesized and used to search for IgE reactivity to sequential epitopes. For indirect mapping, peptide-specific rabbit antibodies were raised to block IgE against surface-exposed epitopes on folded Art v 1. IgE reactivity and basophil activation studies were performed in clinically defined mugwort-allergic patients. Secondary structure of recombinant (r) Art v 1 and peptides was determined by circular dichroism spectroscopy. Results
Mugwort-allergic patients and humanized mice sensitized by allergen inhalation showed IgE reactivity and/or basophil activation mainly to folded, complete Art v 1 but not to unfolded, sequential peptide epitopes. Blocking of allergic patients' IgE with peptide-specific rabbit antisera identified a hitherto unknown major conformational IgE binding site in the C-terminal Art v 1 domain. Conclusions
Identification of the new major conformational IgE binding site on Art v 1, which can be blocked with IgG raised against non-IgE reactive Art v 1 peptides, is an important basis for the development of a hypoallergenic peptide vaccine for mugwort allergy.
科研通智能强力驱动
Strongly Powered by AbleSci AI