The following is a summary of “Widespread monoclonal IgE antibody convergence to an immunodominant, proanaphylactic Ara h 2 epitope in peanut allergy,” published in the January 2024 issue of Allergy & Immunology by Croote, et al.
Human monoclonal IgE antibodies have remained poorly characterized despite their significant role in peanut allergy. For a study, researchers sought to elucidate the sequences, affinities, clonality, and functional attributes of human monoclonal IgE antibodies in peanut allergy.
The SEQ SIFTER discovery platform, based on single-cell RNA sequencing, was employed to analyze samples from allergic individuals representing diverse demographics to identify commonalities in the human IgE response to peanut allergens. Selected antibodies were then recombinantly expressed and characterized for allergen and epitope specificity, affinity, and functional properties.
The study revealed a remarkable convergent evolution of IgE monoclonal antibodies (mAbs) originating from multiple clonal families, including memory B cells and plasmablasts. These antibodies exhibited subnanomolar affinity to the immunodominant peanut allergen Ara h 2, specifically targeting a linear, repetitive motif. Further investigation demonstrated their capability to induce affinity-dependent degranulation of human mast cells and systemic anaphylaxis upon peanut allergen challenge in humanized mice. Reengineered IgGs derived from these mAbs were also shown to inhibit varying degrees of Ara h 2- and peanut-induced mast cell degranulation in allergic plasma sensitization.
The convergent evolution of IgE mAbs in peanut allergy highlighted the identification of immunodominant epitopes on major allergenic proteins. Understanding the functional properties of these antibodies is crucial for developing therapeutics, such as competitive IgG inhibitors, that can effectively compete with endogenous IgE for allergen binding, thereby preventing the allergic cascade upon accidental allergen exposure.
Reference: jacionline.org/article/S0091-6749(23)01196-X/fulltext