Allergome-wide peptide microarrays enable epitope deconvolution in allergen-specific immunotherapy.
Adult
Allergens
/ immunology
Antigens, Plant
/ immunology
Betula
Desensitization, Immunologic
/ methods
Epitope Mapping
Epitopes, B-Lymphocyte
/ immunology
Female
Humans
Immunoglobulin E
/ metabolism
Immunoglobulin Isotypes
/ metabolism
Male
Microarray Analysis
Middle Aged
Peptides
/ immunology
Plant Proteins
/ immunology
Poaceae
Pollen
/ immunology
Rhinitis, Allergic, Seasonal
/ immunology
Allergen
IgE
IgG
IgG(4)
allergen-specific immunotherapy
antibody
epitope
linear epitope
peptide microarray
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
11
12
2019
revised:
22
07
2020
accepted:
04
08
2020
pubmed:
14
8
2020
medline:
23
9
2021
entrez:
14
8
2020
Statut:
ppublish
Résumé
The interaction of allergens and allergen-specific IgE initiates the allergic cascade after crosslinking of receptors on effector cells. Antibodies of other isotypes may modulate such a reaction. Receptor crosslinking requires binding of antibodies to multiple epitopes on the allergen. Limited information is available on the complexity of the epitope structure of most allergens. We sought to allow description of the complexity of IgE, IgG We generated an allergome-wide microarray comprising 731 allergens in the form of more than 172,000 overlapping 16-mer peptides. Allergen recognition by IgE, IgG Extensive induction of linear peptide-specific Phl p 1- and Bet v 1-specific humoral immunity was demonstrated in subjects undergoing a 3-year-long AIT against grass and birch pollen allergy, respectively. Epitope profiles differed between subjects but were largely established already after 1 year of AIT, suggesting that dominant allergen-specific antibody clones remained as important contributors to humoral immunity following their initial establishment during the early phase of AIT. Complex, subject-specific patterns of allergen isoform and group cross-reactivities in the repertoires were observed, patterns that may indicate different levels of protection against different allergen sources. The study highlights the complexity and subject-specific nature of allergen epitopes recognized following AIT. We envisage that epitope deconvolution will be an important aspect of future efforts to describe and analyze the outcomes of AIT in a personalized manner.
Sections du résumé
BACKGROUND
The interaction of allergens and allergen-specific IgE initiates the allergic cascade after crosslinking of receptors on effector cells. Antibodies of other isotypes may modulate such a reaction. Receptor crosslinking requires binding of antibodies to multiple epitopes on the allergen. Limited information is available on the complexity of the epitope structure of most allergens.
OBJECTIVES
We sought to allow description of the complexity of IgE, IgG
METHODS
We generated an allergome-wide microarray comprising 731 allergens in the form of more than 172,000 overlapping 16-mer peptides. Allergen recognition by IgE, IgG
RESULTS
Extensive induction of linear peptide-specific Phl p 1- and Bet v 1-specific humoral immunity was demonstrated in subjects undergoing a 3-year-long AIT against grass and birch pollen allergy, respectively. Epitope profiles differed between subjects but were largely established already after 1 year of AIT, suggesting that dominant allergen-specific antibody clones remained as important contributors to humoral immunity following their initial establishment during the early phase of AIT. Complex, subject-specific patterns of allergen isoform and group cross-reactivities in the repertoires were observed, patterns that may indicate different levels of protection against different allergen sources.
CONCLUSIONS
The study highlights the complexity and subject-specific nature of allergen epitopes recognized following AIT. We envisage that epitope deconvolution will be an important aspect of future efforts to describe and analyze the outcomes of AIT in a personalized manner.
Identifiants
pubmed: 32791163
pii: S0091-6749(20)31108-8
doi: 10.1016/j.jaci.2020.08.002
pii:
doi:
Substances chimiques
Allergens
0
Antigens, Plant
0
Epitopes, B-Lymphocyte
0
Immunoglobulin Isotypes
0
Peptides
0
Plant Proteins
0
Bet v 1 allergen, Betula
126161-14-6
PHLPI protein, Phleum pratense
160227-82-7
Immunoglobulin E
37341-29-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1077-1086Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.