期刊
ALLERGY
卷 74, 期 12, 页码 2382-2393出版社
WILEY
DOI: 10.1111/all.13948
关键词
allergenicity; birch pollen extract; E-1 phytoprostanes; ligand interaction; lysosomal protease inhibition
资金
- Austrian Science Funds [W_01213, P23417, P27589]
- University of Salzburg priority program Allergy-Cancer-BioNano Research Centre
- Doctorate School Plus Program Biomolecules of the University of Salzburg
- Intramural Research Program of the National Institute of Environmental Health Sciences [Z01-ES102906-01]
- Austrian Science Fund (FWF) [P26997, P27589, W1213, P23417] Funding Source: Austrian Science Fund (FWF)
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES102906] Funding Source: NIH RePORTER
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.
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