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

Genghao Chen; Ellen L. Shrock; Mamie Z. Li; Jonathan M. Spergel; Kari C. Nadeau; Jacqueline A. Pongracic; Dale T. Umetsu; Rima Rachid; Andrew J. MacGinnitie; Wanda Phipatanakul; Lynda Schneider; Hans C. Oettgen; Stephen J. Elledge

Cell Reports Medicine (Oct 2021)

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

Genghao Chen,
Ellen L. Shrock,
Mamie Z. Li,
Jonathan M. Spergel,
Kari C. Nadeau,
Jacqueline A. Pongracic,
Dale T. Umetsu,
Rima Rachid,
Andrew J. MacGinnitie,
Wanda Phipatanakul,
Lynda Schneider,
Hans C. Oettgen,
Stephen J. Elledge

Affiliations

Genghao Chen: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA; Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02115, USA
Ellen L. Shrock: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA; Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02115, USA
Mamie Z. Li: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA
Jonathan M. Spergel: Division of Allergy and Immunology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine of University of Pennsylvania, Philadelphia, PA, USA
Kari C. Nadeau: Department of Medicine, Sean N Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USA
Jacqueline A. Pongracic: Division of Pediatric Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USA
Dale T. Umetsu: Division of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Rima Rachid: Division of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Andrew J. MacGinnitie: Division of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Wanda Phipatanakul: Division of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Lynda Schneider: Division of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Hans C. Oettgen: Division of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Stephen J. Elledge: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA; Corresponding author

Journal volume & issue: Vol. 2, no. 10
p. 100410

Abstract

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Summary: Peanut allergy can result in life-threatening reactions and is a major public health concern. Oral immunotherapy (OIT) induces desensitization to food allergens through administration of increasing amounts of allergen. To dissect peanut-specific immunoglobulin E (IgE) and IgG responses in subjects undergoing OIT, we have developed AllerScan, a method that leverages phage-display and next-generation sequencing to identify the epitope targets of peanut-specific antibodies. We observe a striking diversification and boosting of the peanut-specific IgG repertoire after OIT and a reduction in pre-existing IgE levels against individual epitopes. High-resolution epitope mapping reveals shared recognition of public epitopes in Ara h 1, 2, 3, and 7. In individual subjects, OIT-induced IgG specificities overlap extensively with IgE and exhibit strikingly similar antibody footprints, suggesting related clonal lineages or convergent evolution of peanut-specific IgE and IgG B cells. Individual differences in epitope recognition identified via AllerScan could inform safer and more effective personalized immunotherapy.

Published in Cell Reports Medicine

ISSN: 2666-3791 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General)
Website: https://www.cell.com/cell-reports-medicine

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