9CMC

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

Summary for 9CMC

• Entry DOI: 10.2210/pdb9cmc/pdb
• Descriptor: Fab 23P34 heavy chain, Fab 23P34 light chain, Fab 22S1 heavy chain, ... (6 entities in total)
• Functional Keywords: allergy, antibody complex, peanut, allergen
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 20
• Total formula weight: 449055.24

Authors

Pedersen, L.C.,Mueller, G.A.,Min, J. (deposition date: 2024-07-14, release date: 2025-06-11, Last modification date: 2025-06-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.95 Å)