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Multiple roles of Bet v 1 ligands in allergen stabilization and modulation of endosomal protease activity
Author(s) -
Soh Wai Tuck,
Aglas Lorenz,
Mueller Geoffrey A.,
Gilles Stefanie,
Weiss Richard,
Scheiblhofer Sandra,
Huber Sara,
Scheidt Tamara,
Thompson Peter M.,
Briza Peter,
London Robert E.,
TraidlHoffmann Claudia,
Cabrele Chiara,
Brandstetter Hans,
Ferreira Fatima
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13948
Subject(s) - proteases , protease , cathepsin , biochemistry , cysteine protease , chemistry , endosome , cathepsin s , microbiology and biotechnology , biology , enzyme , receptor
Background 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. Methods 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. Results We identified E 1 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 1 phytoprostanes exhibited a dual role by stabilizing Bet v 1 and inhibiting cathepsin protease activity. Conclusion 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.