title: IgE and allergen-specific immunotherapy-induced IgG4recognize similar epitopes of Bet v 1, the major allergen of birch pollen.
abstract: BACKGROUND
  Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G4which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG4specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG4antibodies are developed is under debate.
  
  
  OBJECTIVE
  We sought to analyze the epitope specificities of IgE and IgG4antibodies from sera of patients who received AIT.
  
  
  METHODS
  15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG4were 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/IgG4to 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_11xhad a Bet v 1a - similar secondary and tertiary structure. Monomeric dispersion of rBet v 1a_11xwas concentration and buffer-dependent. Up to 1500-fold increase in the EC50for IgE-mediated mediator release induced by rBet v 1a_11xwas determined. The reduction of IgE and IgG4binding to rBet v 1a_11xwas comparable in 67% (10/15) of sera. Bet v 1a-specific monoclonal antibodies inhibited binding of serum IgE and IgG4to 66.1% and 64.9%, respectively. Serum IgE and IgG4bound specifically to an individual epitope presented by our model protein in 33% (5/15) of sera.
  
  
  CONCLUSIONS
  Patients receiving AIT develop Bet v 1a-specific IgG4which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG4might stimulate the development of epitope-specific diagnostics and therapeutics.
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: N
authors: N
authors: Groh
authors: Department of Biopolymers, University of Bayreuth, Bayreuth, Germany.
authors: C S
authors: CS
authors: von Loetzen
authors: Department of Pathophysiology and Allergy Research and Christian Doppler Laboratory for Immunomodulation, Medical University of Vienna, Vienna, Austria.
authors: B
authors: B
authors: Subbarayal
authors: Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
authors: C
authors: C
authors: Möbs
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: L
authors: L
authors: Vogel
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: A
authors: A
authors: Hoffmann
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: K
authors: K
authors: Fötisch
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: A
authors: A
authors: Koutsouridou
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: S
authors: S
authors: Randow
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: E
authors: E
authors: Völker
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: A
authors: A
authors: Seutter von Loetzen
authors: Department of Biopolymers, University of Bayreuth, Bayreuth, Germany.
authors: P
authors: P
authors: Rösch
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: S
authors: S
authors: Vieths
authors: Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
authors: W
authors: W
authors: Pfützner
authors: Department of Pathophysiology and Allergy Research and Christian Doppler Laboratory for Immunomodulation, Medical University of Vienna, Vienna, Austria.
authors: B
authors: B
authors: Bohle
authors: Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
authors: D
authors: D
authors: Schiller
mesh_terms: D000818:Animals; D052179:Antigens, Plant / Q000276:immunology*; D003888:Desensitization, Immunologic; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000276:immunology / Q000628:therapy
chemical_list: D052179:Antigens, Plant; D000939:Epitopes; D007074:Immunoglobulin G; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E
keywords: Bet v 1; IgE; IgG4; epitope; immunotherapy