9CMC

Crystal structure of the peanut allergen Ara h 2 with two human derived Fab antibodies 22S1 and 23P34

9CMC の概要

• エントリーDOI: 10.2210/pdb9cmc/pdb
• 分子名称: Fab 23P34 heavy chain, Fab 23P34 light chain, Fab 22S1 heavy chain, ... (6 entities in total)
• 機能のキーワード: allergy, antibody complex, peanut, allergen
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 449055.24

構造登録者

Pedersen, L.C.,Mueller, G.A.,Min, J. (登録日: 2024-07-14, 公開日: 2025-06-11, 最終更新日: 2025-06-25)

主引用文献

Marini-Rapoport, O.,Andrieux, L.,Keswani, T.,Zong, G.,Duchen, D.,Yaari, G.,Min, J.,Lytle, I.R.,Rosenberg, A.F.,Fucile, C.,Kobie, J.J.,Piepenbrink, M.S.,Sun, T.,Martin, V.M.,Yuan, Q.,Shreffler, W.G.,Seppo, A.E.,Jarvinen, K.M.,Loeffler, J.R.,Ward, A.B.,Kleinstein, S.H.,Pedersen, L.C.,Fernandez-Quintero, M.L.,Mueller, G.A.,Patil, S.U.
Germline-encoded recognition of peanut underlies development of convergent antibodies in humans.
Sci Transl Med, 17:eadw4148-eadw4148, 2025

PubMed Abstract: Humans develop immunoglobulin G (IgG) antibodies to the foods they consume. In the context of food allergy, allergen-specific IgG antibodies can sequentially class-switch to pathogenic IgE. However, the mechanism underlying the antigenicity of food proteins remains uncharacterized. Here, we identified convergent antibodies arising from different antibody gene rearrangements that bind to the immunodominant peanut allergen Ara h 2 and characterized allelic and junctional constraints on germline antibody specificity. Structurally, we found similar epitope-paratope interactions across multiple gene rearrangements. We demonstrate that these germline-encoded epitope-specific convergent antibodies to peanut occur commonly in the population because of the worldwide prevalence of the relevant gene rearrangements, allelic independence, and junctional malleability. As a result, serum IgG to this public epitope is prevalent among diverse cohorts of nonallergic peanut-consuming infants and peanut-allergic children and adults. This work demonstrates that IgG recognition of dietary antigens can be intrinsically programmed by the germline antibody repertoire.

PubMed: 40498852
DOI: 10.1126/scitranslmed.adw4148

実験手法

X-RAY DIFFRACTION (2.95 Å)