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

• Published in: Clinical and experimental allergy Vol. 47; no. 5; pp. 693 - 703
• Main Authors: Groh, N, von Loetzen, C S, Subbarayal, B, Möbs, C, Vogel, L, Hoffmann, A, Fötisch, K, Koutsouridou, A, Randow, S, Völker, E, Seutter von Loetzen, A, Rösch, P, Vieths, S, Pfützner, W, Bohle, B, Schiller, D
• Format: Journal Article
• Language: English
• Published: England 01-05-2017
• Subjects: Animals; Antigens, Plant - immunology; Desensitization, Immunologic; Epitopes - immunology; Female; Humans; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Male; Mice; Rhinitis, Allergic, Seasonal - blood; Rhinitis, Allergic, Seasonal - immunology; Rhinitis, Allergic, Seasonal - therapy; IgG4; epitope; IgE; immunotherapy; Bet v 1
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.12835

Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G
which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG
specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG
antibodies are developed is under debate.
We sought to analyze the epitope specificities of IgE and IgG
antibodies from sera of patients who received AIT.
15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG
were analyzed. The structural arrangements of recombinant (r)Bet v 1a and rBet v 1a
, 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
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.
rBet v 1a
had a Bet v 1a - similar secondary and tertiary structure. Monomeric dispersion of rBet v 1a
was concentration and buffer-dependent. Up to 1500-fold increase in the EC
for IgE-mediated mediator release induced by rBet v 1a
was determined. The reduction of IgE and IgG
binding to rBet v 1a
was comparable in 67% (10/15) of sera. Bet v 1a-specific monoclonal antibodies inhibited binding of serum IgE and IgG
to 66.1% and 64.9%, respectively. Serum IgE and IgG
bound specifically to an individual epitope presented by our model protein in 33% (5/15) of sera.
Patients receiving AIT develop Bet v 1a-specific IgG
which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG
might stimulate the development of epitope-specific diagnostics and therapeutics.