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

Titel in Übersetzung: Bet v 1 - a Trojan horse for small ligands boosting allergic sensitization?

Claudia Asam, AL Batista, AH Moraes, VS de Paula, FC Almeida, Lorenz Aglas, C Kitzmüller, B Bohle, C Ebner, Fatima Ferreira-Briza, Michael Wallner, AP Valente

    Publikation: Beitrag in FachzeitschriftArtikel

    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 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.

    OriginalspracheEnglisch
    Seiten (von - bis)1083-93
    Seitenumfang11
    FachzeitschriftClinical and Experimental Allergy
    Jahrgang44
    Ausgabenummer8
    DOIs
    PublikationsstatusVeröffentlicht - Aug 2014

    Bibliographische Notiz

    © 2014 John Wiley & Sons Ltd.

    Systematik der Wissenschaftszweige 2012

    • 302 Klinische Medizin
    • 106 Biologie

    Zitieren

    Asam, C., Batista, AL., Moraes, AH., Paula, VS. D., Almeida, FC., Aglas, L., ... Valente, AP. (2014). Bet v 1 - a Trojan horse for small ligands boosting allergic sensitization? Clinical and Experimental Allergy, 44(8), 1083-93. https://doi.org/10.1111/cea.12361