Convergent monoclonal IgE antibodies from peanut allergic patients are multispecific to immunodominant epitopes of unrelated major peanut and tree nut allergens

• Published in: Allergology international
• Main Authors: Kabasser, Stefan, Kalic Kamath, Tanja, Eber, Ernst, Podzhilkova, Aleksandra, Lupinek, Christian, Hemmer, Wolfgang, Bublin, Mugdim, Croote, Derek, Maleki, Soheila J., Breiteneder, Heimo, Hoffmann-Sommergruber, Karin, Radauer, Christian, Bublin, Merima
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 23.06.2025
• Subjects: Allergen; Cross-reactivity; Food allergy; IgE antibody; Peanut allergy; PBS; Food allergy; IgE antibody; SDS-PAGE; Cross-reactivity; Peanut allergy; Allergen; ELISA; mAb
• ISSN: 1323-8930; 1440-1592; 1440-1592
• DOI: 10.1016/j.alit.2025.05.007

Convergent selection has been identified in the IgE antibody repertoires of peanut-allergic individuals, primarily targeting the 2S albumin Ara h 2 and cross-reacting with two other major allergens, the vicilin Ara h 1 and the legumin Ara h 3. In this study, we aimed to investigate the structural and functional basis of this cross-reactivity and its contribution to the co-sensitization to tree nuts often observed in peanut-allergic subjects. Six convergent antibodies, targeting the immunodominant Ara h 2-DPYSPS motif-associated sequence, and their reverted germline version, were produced as human IgG1 and IgE. Antibody specificity to natural and recombinant peanut and tree nut allergens and allergen-derived peptides was evaluated using ELISA, immunoblotting, inhibition tests, and basophil activation assays. The six antibodies showed reactivity to Ara h 1, Ara h 2, Ara h 3 and weak reactivity to tree nut legumins, especially from almond, walnut and Brazil nut. The germline antibody exclusively recognized Ara h 2. Basophils sensitized with the individual antibodies were activated by Ara h 2 at a concentration of 10 ng/ml and at 100-fold higher concentrations by Ara h 1 and Ara h 3, but not by tree nut legumins. The three Ara h 1- and two Ara h 3-derived antibody-binding peptides, with one from each group previously identified as immunodominant, are in close proximity and may contribute to conformational epitopes. The biological activity of affinity-matured cross-reactive antibodies with Ara h 2-associated sequence convergence may explain the high allergenic potency of peanut and clinically irrelevant co-sensitizations to tree nuts commonly observed in peanut-allergic patients. [Display omitted]