Allergome-wide peptide microarrays enable epitope deconvolution in allergen-specific immunotherapy

Maria Mikus, Arash Zandian, Ronald Sjöberg, Carl Hamsten, Björn Forsström, Morgan Andersson, Lennart Greiff, Mathias Uhlén, Mattias Levin, Peter Nilsson, Marianne van Hage, Mats Ohlin

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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, IgG4, and IgG epitope recognition at a global, allergome-wide level during allergen-specific immunotherapy (AIT). 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, IgG4, and IgG was examined in serum samples collected from subjects undergoing AIT against pollen allergy. 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.

Original languageEnglish
Pages (from-to)1077-1086
JournalJournal of Allergy and Clinical Immunology
Issue number3
Early online date2020 Aug 10
Publication statusPublished - 2021

Subject classification (UKÄ)

  • Immunology in the medical area

Free keywords

  • Allergen
  • allergen-specific immunotherapy
  • antibody
  • epitope
  • IgE
  • IgG
  • linear epitope
  • peptide microarray

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