High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy

Peanut allergy affects roughly 2.2% of children and 1.8% of adults in the United States and can cause life-threatening anaphylaxis. The dominant mechanism is IgE antibodies that recognize specific peanut proteins; when those antibodies bind allergen, they trigger mast cells and basophils to release histamine and related mediators. Oral immunotherapy (OIT) — the gradual administration of escalating doses of allergen — is one of the only treatments that can desensitize allergic patients, but exactly which IgE epitopes go down and which IgG epitopes come up during therapy has been hard to see at residue resolution.

To address that gap, the authors built AllerScan, a phage-display library of 397 overlapping 20-mer peptides that tile every 10 amino acids across all 12 peanut allergens listed in the WHO/IUIS Allergen Nomenclature database. To push the resolution further, they added saturation-mutagenesis variants — replacing each residue with every other amino acid — so that IgE and IgG binding could be mapped down to individual amino acid positions. They applied AllerScan to serum from 15 peanut-allergic children enrolled in the PRROTECT clinical trial before and after a course of peanut OIT.

The picture that emerged was not a uniform “antibodies go down” story. After OIT, the peanut-specific IgG repertoire diversified and increased in magnitude, while pre-existing IgE levels against individual epitopes decreased. Across patients, certain “public” epitopes in the major allergens Ara h 1, 2, 3, and 7 were recognized in common. Within individual subjects, OIT-induced IgG specificities overlapped extensively with the patient’s IgE specificities and exhibited strikingly similar antibody footprints, suggesting related clonal lineages or convergent evolution of peanut-specific IgE and IgG B cells. The residue-level granularity opens a path toward safer, personalized OIT regimens guided by each patient’s epitope-specific antibody repertoire.