title: Naturally occurring hypoallergenic Bet v 1 isoforms fail to induce IgE responses in individuals with birch pollen allergy.
abstract: BACKGROUND
  Engineered hypoallergens are currently being investigated for specific immunotherapy of allergic diseases in preclinical and clinical studies. Naturally occurring hypoallergens have by and large not been considered as a source of vaccine candidates.
  
  
  OBJECTIVE
  Evaluation of the antibody response in atopic individuals induced by birch pollen containing isoforms of the major birch pollen allergen Bet v 1.
  
  
  METHODS
  Isoform-specific antibody isotype responses for Bet v 1.0101, Bet v 1.0401, and Bet v 1.1001 were determined for 35 sera of individuals with birch pollen allergy. Isoform structures were compared and related to IgE-binding inhibitory capacities and induction of mediator release in human Fcvarepsilon receptor transformed rat basophilic leukemia cells.
  
  
  RESULTS
  Bet v 1.0101 induced a predominant IgE response, whereas the significant highest levels of IgG(4) antibodies were directed against Bet v 1.0401. Bet v 1.1001 induced only a minimal antibody response. Structural comparisons revealed that most of the amino acid differences between the isoforms were located on the protein surfaces. IgE induced by Bet v 1.0101 only partly cross-reacted with the 2 other isoforms and bound to them with notably lower affinity. Bet v 1.0401 and Bet v 1.1001 also were poor inducers of mediator release.
  
  
  CONCLUSIONS
  Bet v 1 isoforms possess highly variant immunogenic and allergenic properties. Bet v 1.0101 acts as the sensitizing agent, whereas Bet v 1.0401 and Bet v 1.1001 can induce only a minimal IgE response.
authors: Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
authors: Stefan
authors: S
authors: Wagner
authors: Christian
authors: C
authors: Radauer
authors: Merima
authors: M
authors: Bublin
authors: Karin
authors: K
authors: Hoffmann-Sommergruber
authors: Tamara
authors: T
authors: Kopp
authors: Elli K
authors: EK
authors: Greisenegger
authors: Lothar
authors: L
authors: Vogel
authors: Stefan
authors: S
authors: Vieths
authors: Otto
authors: O
authors: Scheiner
authors: Heimo
authors: H
authors: Breiteneder
mesh_terms: D000328:Adult; D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000097:blood; D052179:Antigens, Plant; D029662:Betula / Q000276:immunology; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000517:prevention & control; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology*; D011058:Pollen / Q000009:adverse effects / Q000276:immunology; D020033:Protein Isoforms / Q000737:chemistry / Q000276:immunology*; D051381:Rats
chemical_list: D000485:Allergens; D019138:Antibodies, Blocking; D052179:Antigens, Plant; D007074:Immunoglobulin G; D010940:Plant Proteins; D020033:Protein Isoforms; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E