High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy
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 s...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2021-10-01
|
Series: | Cell Reports Medicine |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379121002688 |
_version_ | 1819026396785147904 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Genghao Chen |
collection | DOAJ |
description | 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. |
first_indexed | 2024-12-21T05:25:55Z |
format | Article |
id | doaj.art-393b68bda2814b4c96490fe3b2cb72c0 |
institution | Directory Open Access Journal |
issn | 2666-3791 |
language | English |
last_indexed | 2024-12-21T05:25:55Z |
publishDate | 2021-10-01 |
publisher | Elsevier |
record_format | Article |
series | Cell Reports Medicine |
spelling | doaj.art-393b68bda2814b4c96490fe3b2cb72c02022-12-21T19:14:41ZengElsevierCell Reports Medicine2666-37912021-10-01210100410High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapyGenghao Chen0Ellen L. Shrock1Mamie Z. Li2Jonathan M. Spergel3Kari C. Nadeau4Jacqueline A. Pongracic5Dale T. Umetsu6Rima Rachid7Andrew J. MacGinnitie8Wanda Phipatanakul9Lynda Schneider10Hans C. Oettgen11Stephen J. Elledge12Department 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, USADepartment 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, USADepartment 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, USADivision 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, USADepartment of Medicine, Sean N Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USADivision 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, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666379121002688peanut allergyantibodyantibody repertoirephage displayoral immunotherapyfood allergy |
spellingShingle | 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 High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy Cell Reports Medicine peanut allergy antibody antibody repertoire phage display oral immunotherapy food allergy |
title | High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy |
title_full | High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy |
title_fullStr | High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy |
title_full_unstemmed | High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy |
title_short | High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy |
title_sort | high resolution epitope mapping by allerscan reveals relationships between ige and igg repertoires during peanut oral immunotherapy |
topic | peanut allergy antibody antibody repertoire phage display oral immunotherapy food allergy |
url | http://www.sciencedirect.com/science/article/pii/S2666379121002688 |
work_keys_str_mv | AT genghaochen highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT ellenlshrock highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT mamiezli highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT jonathanmspergel highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT karicnadeau highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT jacquelineapongracic highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT daletumetsu highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT rimarachid highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT andrewjmacginnitie highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT wandaphipatanakul highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT lyndaschneider highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT hanscoettgen highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy AT stephenjelledge highresolutionepitopemappingbyallerscanrevealsrelationshipsbetweenigeandiggrepertoiresduringpeanutoralimmunotherapy |