Bet v 1 – a Trojan horse for small ligands boosting allergic sensitization?. Issue 8 (August 2014)

• Record Type: Journal Article
• Authors: Asam, C.; Batista, A. L.; Moraes, A. H.; de Paula, V. S.; Almeida, F. C. L.; Aglas, L.; Kitzmüller, C.; Bohle, B.; Ebner, C.; Ferreira, F.; Wallner, M.; Valente, A. P.
• Is Part Of: Clinical & experimental allergy. Volume 44:Issue 8(2014:Aug.)
• Page Start: 1083
• Page End: 1093
• Publication Date: 2014-08
• Subjects: Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.12361
• Languages: English
• ISSNs: 0954-7894

Abstract

<abstract abstract-type="main" id="cea12361-abs-0001"> <title>Summary</title> <sec id="cea12361-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="cea12361-sec-0002" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="cea12361-sec-0003" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="cea12361-sec-0004" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="cea12361-sec-0005" sec-type="section"> <title>Conclusions and clinical relevance</title> <p>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.</p> </sec> </abstract>