Kinetics, cross-reactivity, and specificity of Bet v 1-specific IgG4 antibodies induced by immunotherapy with birch pollen

Allergy. 2013 Nov;68(11):1377-86. doi: 10.1111/all.12236. Epub 2013 Sep 21.


Background: IgE antibodies specific for the major birch pollen allergen frequently cross-react with Bet v 1 homologous food proteins, for example Cor a 1 in hazelnut and Mal d 1 in apple. Specific immunotherapy with birch pollen (BP-SIT) induces IgG4 antibodies that inhibit IgE binding to Bet v 1. However, information on cross-reactivity of BP-SIT-induced Bet v 1-specific IgG4 antibodies with food allergens is limited. In this study, we investigated the kinetics of production, cross-reactivity, and IgE-blocking activity of Bet v 1-specific IgG4 antibodies emerging during conventional BP-SIT and whether IgG4-epitopes overlapped with IgE epitopes.

Methods: IgE and IgG4 levels specific for Bet v 1, Mal d 1, and Cor a 1 were determined in 42 birch pollen-allergic patients before and during BP-SIT. Inhibition of IgE binding was studied by IgE-facilitated antigen-binding assays and basophil activation tests. Furthermore, inhibition of IgE-mediated activation of food allergen-reactive Bet v 1-specific T-cell lines was assessed. Competitive immunoscreening of phage-displayed peptides was applied to select mimotopes recognized by IgE and IgG4 antibodies, respectively. The resulting mimotopes were mapped on the surface of the 3D structure of the allergens using a computer-based algorithm.

Results: BP-SIT significantly increased Bet v 1- and food allergen-reactive IgG4 antibodies. In parallel, allergen-specific IgE levels decreased significantly. Sera containing food allergen-reactive IgG4 antibodies inhibited IgE binding, basophil activation, and IgE-mediated food allergen-induced T-cell proliferation. Predicted IgE and IgG4 epitopes on all allergens showed high overlap.

Conclusion: Our results indicate that BP-SIT may induce Bet v 1-specific IgG4 antibodies that cross-react with related food allergens and inhibit IgE binding by epitope competition.

Keywords: IgE; IgG4; birch pollen allergy; blocking antibodies; specific immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allergens / immunology*
  • Antibodies, Blocking / drug effects
  • Antibody Specificity / immunology*
  • Antigens, Plant / administration & dosage
  • Antigens, Plant / immunology*
  • Antigens, Plant / metabolism
  • Betula / immunology*
  • Cell Line
  • Child
  • Cross Reactions / immunology
  • Desensitization, Immunologic / methods*
  • Food Hypersensitivity / immunology*
  • Humans
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin E / metabolism
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin G / metabolism
  • Middle Aged
  • Pollen / immunology*
  • Young Adult


  • Allergens
  • Antibodies, Blocking
  • Antigens, Plant
  • Immunoglobulin G
  • Bet v 1 allergen, Betula
  • Immunoglobulin E