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

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title = "Allergome-wide peptide microarrays enable epitope deconvolution in allergen-specific immunotherapy",
abstract = "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.",
keywords = "Allergen, allergen-specific immunotherapy, antibody, epitope, IgE, IgG, linear epitope, peptide microarray",
author = "Maria Mikus and Arash Zandian and Ronald Sj{\"o}berg and Carl Hamsten and Bj{\"o}rn Forsstr{\"o}m and Morgan Andersson and Lennart Greiff and Mathias Uhl{\'e}n and Mattias Levin and Peter Nilsson and {van Hage}, Marianne and Mats Ohlin",
year = "2020",
month = aug,
day = "10",
doi = "10.1016/j.jaci.2020.08.002",
language = "English",
journal = "Journal of Allergy and Clinical Immunology",
issn = "1097-6825",
publisher = "Elsevier",