title: Bet v 1--a Trojan horse for small ligands boosting allergic sensitization?
abstract: BACKGROUND
  Birch pollen allergy represents the main cause of winter and spring pollinosis in the temperate climate zone of the northern hemisphere and sensitization towards Bet v 1, the major birch pollen allergen, affects over 100 million allergic patients. The major birch pollen allergen Bet v 1 has been described as promiscuous acceptor for a wide variety of hydrophobic ligands.
  
  
  OBJECTIVE
  In search of intrinsic properties of Bet v 1, which account responsible for the high allergenic potential of the protein, we thought to investigate the effects of ligand-binding on immunogenic as well as allergenic properties.
  
  
  METHODS
  As surrogate ligand of Bet v 1 sodium deoxycholate (DOC) was selected. Recombinant and natural Bet v 1 were characterised physico-chemically as well as immunologically in the presence or absence of DOC, and an animal model of allergic sensitization was established. Moreover, human IgE binding to Bet v 1 was analysed by nuclear magnetic resonance (NMR) spectroscopy.
  
  
  RESULTS
  Ligand-binding had an overall stabilizing effect on Bet v 1. This translated in a Th2 skewing of the immune response in a mouse model. Analyses of human IgE binding on Bet v 1 in mediator release assays revealed that ligand-bound allergen-induced degranulation at lower concentrations; however, in basophil activation tests with human basophils ligand-binding did not show this effect. For the first time, human IgE epitopes on Bet v 1 were determined using antibodies isolated from patients' sera. The IgE epitope mapping of Bet v 1 demonstrated the presence of multiple binding regions.
  
  
  CONCLUSIONS
  Deoxycholate binding stabilizes conformational IgE epitopes on Bet v 1; however, the epitopes themselves remain unaltered. Therefore, we speculate that humans are exposed to both ligand-bound and free Bet v 1 during sensitization, disclosing the ligand-binding cavity of the allergen as key structural element.
authors: Christian Doppler Laboratory for Allergy Diagnosis and Therapy, University of Salzburg, Salzburg, Austria.
authors: C
authors: C
authors: Asam
authors: A L
authors: AL
authors: Batista
authors: A H
authors: AH
authors: Moraes
authors: V S
authors: VS
authors: de Paula
authors: F C L
authors: FC
authors: Almeida
authors: L
authors: L
authors: Aglas
authors: C
authors: C
authors: Kitzmüller
authors: B
authors: B
authors: Bohle
authors: C
authors: C
authors: Ebner
authors: F
authors: F
authors: Ferreira
authors: M
authors: M
authors: Wallner
authors: A P
authors: AP
authors: Valente
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D052179:Antigens, Plant / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015549:Basophil Degranulation Test; D001491:Basophils / Q000276:immunology; D029662:Betula / Q000009:adverse effects*; D015550:Cell Degranulation / Q000276:immunology; D002460:Cell Line; D003840:Deoxycholic Acid / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology / Q000302:isolation & purification; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D011058:Pollen / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D013816:Thermodynamics
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D000939:Epitopes; D008024:Ligands; D011994:Recombinant Proteins; D003840:Deoxycholic Acid; D007073:Immunoglobulin E
keywords: Bet v 1; IgE reactivity; NMR; allergenicity; allergic sensitization; epitope mapping; human IgE epitope