Bet v 1 – a Trojan horse for small ligands boosting allergic sensitization?

<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats: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.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats: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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>As surrogate ligand of Bet v 1 sodium deoxycholate (<jats:styled-content style="fixed-case">DOC</jats:styled-content>) was selected. Recombinant and natural Bet v 1 were characterised physico‐chemically as well as immunologically in the presence or absence of <jats:styled-content style="fixed-case">DOC</jats:styled-content>, and an animal model of allergic sensitization was established. Moreover, human IgE binding to Bet v 1 was analysed by nuclear magnetic resonance (<jats:styled-content style="fixed-case">NMR</jats:styled-content>) spectroscopy.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats: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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and clinical relevance</jats:title><jats: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.</jats:p></jats:sec>