Multiple roles of Bet v 1 ligands in allergen stabilization and modulation of endosomal protease activity

Wai Tuck Soh, Lorenz Aglas, Geoffrey A Mueller, Stefanie Gilles, Richard Weiss, Sandra Scheiblhofer, Sara Huber, Tamara Scheidt, Peter M Thompson, Peter Briza, Robert E London, Claudia Traidl-Hoffmann, Chiara Cabrele, Hans Brandstetter, Fatima Ferreira

Publikation: Beitrag in FachzeitschriftArtikel

Abstract

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 E1 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. E1 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.
OriginalspracheEnglisch
FachzeitschriftAllergy: European Journal of Allergy and Clinical Immunology
Frühes Online-Datum22 Jun 2019
DOIs
PublikationsstatusVeröffentlicht - 2019

Bibliographische Notiz

© 2019 The Authors. Allergy published by John Wiley & Sons Ltd.

Systematik der Wissenschaftszweige 2012

  • 106 Biologie

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