Journal
CLINICAL AND EXPERIMENTAL ALLERGY
Volume 44, Issue 8, Pages 1083-1093Publisher
WILEY
DOI: 10.1111/cea.12361
Keywords
allergenicity; allergic sensitization; allergic sensitization; Bet v 1; epitope mapping; human IgE epitope; IgE reactivity; NMR
Categories
Funding
- Christian Doppler Research Association, Austria
- Biomay AG, Vienna, Austria
- Austrian Science Fund (FWF) [P 23417-B13]
- CNPq
- FAPERJ
- CAPES
- INBEB, Brazil
- Austrian Science Fund (FWF) [P 23417] Funding Source: researchfish
- Austrian Science Fund (FWF) [W1213] Funding Source: Austrian Science Fund (FWF)
Ask authors/readers for more resources
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 and clinical relevance 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available