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.
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.
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Authors: Martina Di Muzio; Sabrina Wildner; Sara Huber; Michael Hauser; Eva Vejvar; Werner Auzinger; Christof Regl; Josef Laimer; Danila Zennaro; Nicole Wopfner; Christian G Huber; Ronald van Ree; Adriano Mari; Peter Lackner; Fatima Ferreira; Mario Schubert; Gabriele Gadermaier Journal: J Biol Chem Date: 2020-10-09 Impact factor: 5.157
Authors: A H Moraes; C Asam; A Batista; F C L Almeida; M Wallner; F Ferreira; A P Valente Journal: Biomol NMR Assign Date: 2015-08-20 Impact factor: 0.746
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Authors: Sarina Grutsch; Julian E Fuchs; Regina Freier; Stefan Kofler; Marium Bibi; Claudia Asam; Michael Wallner; Fátima Ferreira; Hans Brandstetter; Klaus R Liedl; Martin Tollinger Journal: Biophys J Date: 2014-12-16 Impact factor: 4.033
Authors: Yoan Machado; Regina Freier; Sandra Scheiblhofer; Theresa Thalhamer; Melissa Mayr; Peter Briza; Sarina Grutsch; Linda Ahammer; Julian E Fuchs; Hannes G Wallnoefer; Almedina Isakovic; Vera Kohlbauer; Arthur Hinterholzer; Markus Steiner; Martin Danzer; Jutta Horejs-Hoeck; Fatima Ferreira; Klaus R Liedl; Martin Tollinger; Peter Lackner; Christopher M Johnson; Hans Brandstetter; Josef Thalhamer; Richard Weiss Journal: J Allergy Clin Immunol Date: 2015-11-11 Impact factor: 10.793