Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Kabasser, S; Kalic, Kamath, T; Eber, E; Podzhilkova, A; Lupinek, C; Hemmer, W; Bublin, M; Croote, D; Maleki, SJ; Breiteneder, H; Hoffmann-Sommergruber, K; Radauer, C; Bublin, M.
Convergent monoclonal IgE antibodies from peanut allergic patients are multispecific to immunodominant epitopes of unrelated major peanut and tree nut allergens.
Allergol Int. 2025;
Doi: 10.1016/j.alit.2025.05.007
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Eber Ernst
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.