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

Single-amino-acid-resolution mapping of peanut-specific IgE and IgG epitopes in 15 children undergoing oral immunotherapy.

Chen G, Shrock EL, Li MZ, Spergel JM, Nadeau KC, Pongracic JA, Umetsu DT, Rachid R, MacGinnitie AJ, Phipatanakul W, Schneider L, Oettgen HC, Elledge SJ.

Cell Reports Medicine · October 19, 2021 · DOI: 10.1016/j.xcrm.2021.100410

How to cite

AMA

Chen G, Shrock EL, Li MZ, et al. High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy. Cell Rep Med. 2021;2(10):100410. doi:10.1016/j.xcrm.2021.100410

APA

Chen, G., Shrock, E. L., Li, M. Z., Spergel, J. M., Nadeau, K. C., Pongracic, J. A., Umetsu, D. T., Rachid, R., MacGinnitie, A. J., Phipatanakul, W., Schneider, L., Oettgen, H. C., & Elledge, S. J. (2021). High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy. Cell Reports Medicine, 2(10), 100410. https://doi.org/10.1016/j.xcrm.2021.100410

BibTeX

@article{chen2021allerscan,
  title   = {High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy},
  author  = {Chen, Genghao and Shrock, Ellen L. and Li, Mamie Z. and Spergel, Jonathan M. and Nadeau, Kari C. and Pongracic, Jacqueline A. and Umetsu, Dale T. and Rachid, Rima and MacGinnitie, Andrew J. and Phipatanakul, Wanda and Schneider, Lynda and Oettgen, Hans C. and Elledge, Stephen J.},
  journal = {Cell Reports Medicine},
  volume  = {2},
  number  = {10},
  pages   = {100410},
  year    = {2021},
  doi     = {10.1016/j.xcrm.2021.100410}
}

Peanut oral immunotherapy (OIT) is one of the only therapies that can desensitize peanut-allergic patients, yet what actually happens to a patient’s antibody repertoire during treatment had been hard to see at residue-level resolution. The Larman and Elledge labs introduce AllerScan — a phage-display plus next-generation sequencing platform that maps peanut-specific IgE and IgG epitopes across all 12 WHO/IUIS-listed peanut allergens at single-amino-acid resolution — and apply it to 15 peanut-allergic children enrolled in the PRROTECT clinical trial.

Read publication at Cell Reports Medicine

In this publication:

AllerScan tiles 397 overlapping 20-mer peptides every 10 amino acids across all 12 WHO/IUIS peanut allergens, plus saturation-mutagenesis variants for residue-by-residue resolution.
15 peanut-allergic children in the PRROTECT clinical trial were profiled before and after oral immunotherapy, capturing IgE and IgG epitope reshaping at single-amino-acid resolution.
OIT diversified and boosted the peanut-specific IgG repertoire while reducing pre-existing IgE levels against individual epitopes.
Public epitopes in major allergens Ara h 1, 2, 3, and 7 were recognized across patients; OIT-induced IgG specificities overlapped extensively with IgE, suggesting related clonal lineages or convergent B-cell evolution.

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.

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

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