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Clin Exp Allergy. 2017 May;47(5):693-703. doi: 10.1111/cea.12835. Epub 2016 Nov 28.

IgE and allergen-specific immunotherapy-induced IgG4 recognize similar epitopes of Bet v 1, the major allergen of birch pollen.

Author information

1
Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
2
Department of Biopolymers, University of Bayreuth, Bayreuth, Germany.
3
Department of Pathophysiology and Allergy Research and Christian Doppler Laboratory for Immunomodulation, Medical University of Vienna, Vienna, Austria.
4
Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.

Abstract

BACKGROUND:

Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G4 which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG4 specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG4 antibodies are developed is under debate.

OBJECTIVE:

We sought to analyze the epitope specificities of IgE and IgG4 antibodies from sera of patients who received AIT.

METHODS:

15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG4 were analyzed. The structural arrangements of recombinant (r)Bet v 1a and rBet v 1a_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/IgG4 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_11x had a Bet v 1a - similar secondary and tertiary structure. Monomeric dispersion of rBet v 1a_11x was concentration and buffer-dependent. Up to 1500-fold increase in the EC50 for IgE-mediated mediator release induced by rBet v 1a_11x was determined. The reduction of IgE and IgG4 binding to rBet v 1a_11x was comparable in 67% (10/15) of sera. Bet v 1a-specific monoclonal antibodies inhibited binding of serum IgE and IgG4 to 66.1% and 64.9%, respectively. Serum IgE and IgG4 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 IgG4 which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG4 might stimulate the development of epitope-specific diagnostics and therapeutics.

KEYWORDS:

Bet v 1; IgE; IgG4; epitope; immunotherapy

PMID:
27770477
DOI:
10.1111/cea.12835
[Indexed for MEDLINE]

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