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- W4386987277 abstract "Despite their central role in peanut allergy, human monoclonal IgE antibodies have eluded characterization.We sought to define the sequences, affinities, clonality, and functional properties of human monoclonal IgE antibodies in peanut allergy.We applied our single-cell RNA-sequencing-based SEQ SIFTER™ discovery platform to a set of allergic individuals that varied by age, sex, ethnicity, and geographic location in order to understand commonalities in the human IgE response to peanut allergens. Select antibodies were then recombinantly expressed and characterized for their allergen and epitope specificity, affinity, and functional properties.We found striking convergent evolution of IgE mAbs from several clonal families comprising both memory B cells and plasmablasts. These antibodies bound with sub-nanomolar affinity to the immunodominant peanut allergen Ara h 2, specifically a linear, repetitive motif. Further characterization of these mAbs revealed their ability to single-handedly cause affinity-dependent degranulation of human mast cells and systemic anaphylaxis upon peanut allergen challenge in humanized mice. Lastly, we demonstrate these mAbs, re-engineered as IgGs, inhibit significant, but variable, amounts of Ara h 2- and peanut-mediated degranulation of mast cells sensitized with allergic plasma.Convergent evolution of IgE mAbs in peanut allergy is a common phenomenon that can reveal immunodominant epitopes on major allergenic proteins. Understanding the functional properties of these molecules is key to developing therapeutics, such as competitive IgG inhibitors, that are able to stoichiometrically outcompete endogenous IgE for allergen and thereby prevent the allergic cascade in the case of accidental allergen exposure." @default.
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- W4386987277 date "2023-09-01" @default.
- W4386987277 modified "2023-09-27" @default.
- W4386987277 title "Widespread monoclonal IgE antibody convergence to an immunodominant, pro-anaphylactic Ara h 2 epitope in peanut allergy" @default.
- W4386987277 doi "https://doi.org/10.1016/j.jaci.2023.08.035" @default.
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