IgE and allergen-specific immunotherapy-induced IgG sub(4) recognize similar epitopes of Bet v 1, the major allergen of birch pollen

• Published in: Clinical and experimental allergy 2017-05, Vol.47 (5), p.693-703
• Main Authors: Groh, N, Loetzen, C S, Subbarayal, B, Mobs, C, Vogel, L, Hoffmann, A, Fotisch, K, Koutsouridou, A, Randow, S, Volker, E, Seutter von Loetzen, A, Rosch, P, Vieths, S, Pfuetzner, W, Bohle, B, Schiller, D
• Format: Article
• Language: English
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.12835

Background Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G sub(4) which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG sub(4) specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG sub(4) antibodies are developed is under debate. Objective We sought to analyze the epitope specificities of IgE and IgG sub(4) antibodies from sera of patients who received AIT. Methods 15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG sub(4) were analyzed. The structural arrangements of recombinant (r)Bet v 1a and rBet v 1a sub(_11x), modified in five potential epitopes, were analyzed by circular dichroism and nuclear magnetic resonance spectroscopy. IgE binding to Bet v 1 was assessed by ELISA and mediator release assays. Competitive binding of monoclonal antibodies specific for Bet v 1a and serum IgE/IgG sub(4) to rBet v 1a and serum antibody binding to a non-allergenic Bet v 1-type model protein presenting an individual epitope for IgE was analyzed in ELISA and western blot. Results rBet v 1a sub(_11x) had a Bet v 1a - similar secondary and tertiary structure. Monomeric dispersion of rBet v 1a sub(_11x) was concentration and buffer-dependent. Up to 1500-fold increase in the EC sub(50) for IgE-mediated mediator release induced by rBet v 1a sub(_11x) was determined. The reduction of IgE and IgG sub(4) binding to rBet v 1a sub(_11x) was comparable in 67% (10/15) of sera. Bet v 1a-specific monoclonal antibodies inhibited binding of serum IgE and IgG sub(4) to 66.1% and 64.9%, respectively. Serum IgE and IgG sub(4) bound specifically to an individual epitope presented by our model protein in 33% (5/15) of sera. Conclusion and Clinical Relevance Patients receiving AIT develop Bet v 1a-specific IgG sub(4) which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG sub(4) might stimulate the development of epitope-specific diagnostics and therapeutics.