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

Authors

  • C. Asam,

    1. Christian Doppler Laboratory for Allergy Diagnosis and Therapy, University of Salzburg, Salzburg, Austria
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  • A. L. Batista,

    1. Programa de Biologia Estrutural, Instituto de Bioquímica Médica, Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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  • A. H. Moraes,

    1. Programa de Biologia Estrutural, Instituto de Bioquímica Médica, Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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  • V. S. de Paula,

    1. Programa de Biologia Estrutural, Instituto de Bioquímica Médica, Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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  • F. C. L. Almeida,

    1. Programa de Biologia Estrutural, Instituto de Bioquímica Médica, Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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  • L. Aglas,

    1. Christian Doppler Laboratory for Allergy Diagnosis and Therapy, University of Salzburg, Salzburg, Austria
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  • C. Kitzmüller,

    1. Christian Doppler Laboratory for Immunomodulation, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
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  • B. Bohle,

    1. Christian Doppler Laboratory for Immunomodulation, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
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  • C. Ebner,

    1. Allergieambulatorium Reumannplatz, Vienna, Austria
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  • F. Ferreira,

    1. Christian Doppler Laboratory for Allergy Diagnosis and Therapy, University of Salzburg, Salzburg, Austria
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  • M. Wallner,

    Corresponding author
    1. Christian Doppler Laboratory for Allergy Diagnosis and Therapy, University of Salzburg, Salzburg, Austria
    • Correspondence:

      Prof. Dr Ana Paula Valente, Responsible for NMR experiments, National NMR Center, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco K, CNRMN, Rio de Janeiro, RJ 21941-902, Brasil.

      E-mail: valente@cnrmn.bioqmed.ufrj.br

      and

      Dr Michael Wallner, Responsible for allergy and immunology experiments, Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Hellbrunnerstr. 34, A-5020 Salzburg, Austria.

      E-mail: michael.wallner@sbg.ac.at

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  • A. P. Valente

    Corresponding author
    1. Programa de Biologia Estrutural, Instituto de Bioquímica Médica, Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
    • Correspondence:

      Prof. Dr Ana Paula Valente, Responsible for NMR experiments, National NMR Center, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco K, CNRMN, Rio de Janeiro, RJ 21941-902, Brasil.

      E-mail: valente@cnrmn.bioqmed.ufrj.br

      and

      Dr Michael Wallner, Responsible for allergy and immunology experiments, Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Hellbrunnerstr. 34, A-5020 Salzburg, Austria.

      E-mail: michael.wallner@sbg.ac.at

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Summary

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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