8DB4

Crystal structure of the peanut allergen Ara h 2 bound by two neutralizing antibodies 22S1 and 13T1

8DB4 の概要

• エントリーDOI: 10.2210/pdb8db4/pdb
• 分子名称: 13T1 Heavy chain, 13T1 Light chain, 22S1 Heavy chain, ... (8 entities in total)
• 機能のキーワード: antibody, immunotherapy, immunoglobulin, allergen-immune system complex, allergen/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 223644.62

構造登録者

Min, J.,Pedersen, L.C. (登録日: 2022-06-14, 公開日: 2023-01-25, 最終更新日: 2024-11-06)

主引用文献

LaHood, N.A.,Min, J.,Keswani, T.,Richardson, C.M.,Amoako, K.,Zhou, J.,Marini-Rapoport, O.,Bernard, H.,Hazebrouck, S.,Shreffler, W.G.,Love, J.C.,Pomes, A.,Pedersen, L.C.,Mueller, G.A.,Patil, S.U.
Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy.
J.Clin.Invest., 133:-, 2023

PubMed Abstract: In IgE-mediated food allergies, exposure to the allergen activates systemic allergic responses. Oral immunotherapy (OIT) treats food allergies through incremental increases in oral allergen exposure. However, OIT only induces sustained clinical tolerance and decreased basophil sensitivity in a subset of individuals despite increases in circulating allergen-specific IgG in all treated individuals. Therefore, we examined the allergen-specific antibodies from 2 OIT cohorts of patients with sustained and transient responses. Here, we compared antibodies from individuals with sustained or transient responses and discovered specific tolerance-associated conformational epitopes of the immunodominant allergen Ara h 2 recognized by neutralizing antibodies. First, we identified what we believe to be previously unknown conformational, intrahelical epitopes using x-ray crystallography with recombinant antibodies. We then identified epitopes only recognized in sustained tolerance. Finally, antibodies recognizing tolerance-associated epitopes effectively neutralized allergen to suppress IgE-mediated effector cell activation. Our results demonstrate the molecular basis of antibody-mediated protection in IgE-mediated food allergy, by defining how these antibodies disrupt IgE-allergen interactions to prevent allergic reactions. Our approach to studying the structural and functional basis for neutralizing antibodies demonstrates the clinical relevance of specific antibody clones in antibody-mediated tolerance. We anticipate that our findings will form the foundation for treatments of peanut allergy using neutralizing antibodies and hypoallergens.

PubMed: 36647835
DOI: 10.1172/JCI164501

実験手法

X-RAY DIFFRACTION (2.3 Å)