Multiple roles of Bet v 1 ligands in allergen stabilization and modulation of endosomal protease activity
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- Wai Tuck Soh
- Department of Biosciences University of Salzburg Salzburg Austria
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- Lorenz Aglas
- Department of Biosciences University of Salzburg Salzburg Austria
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- Geoffrey A. Mueller
- Department of Health and Human Services, Genome Integrity and Structural Biology Laboratory National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park North Carolina
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- Stefanie Gilles
- Institute of Environmental Medicine UNIKA‐T, Technical University Munich and Helmholtz Zentrum München Augsburg Germany
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- Richard Weiss
- Department of Biosciences University of Salzburg Salzburg Austria
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- Sandra Scheiblhofer
- Department of Biosciences University of Salzburg Salzburg Austria
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- Sara Huber
- Department of Biosciences University of Salzburg Salzburg Austria
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- Tamara Scheidt
- Department of Biosciences University of Salzburg Salzburg Austria
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- Peter M. Thompson
- Department of Health and Human Services, Genome Integrity and Structural Biology Laboratory National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park North Carolina
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- Peter Briza
- Department of Biosciences University of Salzburg Salzburg Austria
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- Robert E. London
- Department of Health and Human Services, Genome Integrity and Structural Biology Laboratory National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park North Carolina
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- Claudia Traidl‐Hoffmann
- Institute of Environmental Medicine UNIKA‐T, Technical University Munich and Helmholtz Zentrum München Augsburg Germany
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- Chiara Cabrele
- Department of Biosciences University of Salzburg Salzburg Austria
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- Hans Brandstetter
- Department of Biosciences University of Salzburg Salzburg Austria
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- Fatima Ferreira
- Department of Biosciences University of Salzburg Salzburg Austria
説明
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Over 100 million people worldwide suffer from birch pollen allergy. Bet v 1 has been identified as the major birch pollen allergen. However, the molecular mechanisms of birch allergic sensitization, including the roles of Bet v 1 and other components of the birch pollen extract, remain incompletely understood. Here, we examined how known birch pollen–derived molecules influence the endolysosomal processing of Bet v 1, thereby shaping its allergenicity.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We analyzed the biochemical and immunological interaction of ligands with Bet v 1. We then investigated the proteolytic processing of Bet v 1 by endosomal extracts in the presence and absence of ligands, followed by a detailed kinetic analysis of Bet v 1 processing by individual endolysosomal proteases as well as the T‐cell epitope presentation in BMDCs.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We identified E<jats:sub>1</jats:sub> phytoprostanes as novel Bet v 1 ligands. Pollen‐derived ligands enhanced the proteolytic resistance of Bet v 1, affecting degradation kinetics and preferential cleavage sites of the endolysosomal proteases cathepsin S and legumain. E<jats:sub>1</jats:sub> phytoprostanes exhibited a dual role by stabilizing Bet v 1 and inhibiting cathepsin protease activity.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Bet v 1 can serve as a transporter of pollen‐derived, bioactive compounds. When carried to the endolysosome, such compounds can modulate the proteolytic activity, including its processing by cysteine cathepsins. We unveil a paradigm shift from an allergen‐centered view to a more systemic view that includes the host endolysosomal enzymes.</jats:p></jats:sec>
収録刊行物
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- Allergy
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Allergy 74 (12), 2382-2393, 2019-10-08
Wiley