Abstract
BackgroundOver 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.MethodsWe 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.ResultsWe 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.ConclusionBet 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.
Highlights
An allergic response is a two-step process, involving an initial sensitization step characterized by a pronounced Th2 polarization and followed by an acute antibody recognition step.[1]
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
Summary
An allergic response is a two-step process, involving an initial sensitization step characterized by a pronounced Th2 polarization and followed by an acute antibody recognition step.[1]. Three major groups of compounds have been proposed to interact or cooperate with Bet_v_1, two of which are pollen-derived: (i) flavonoids, (ii) phytohormones, and (iii) microbe-derived Toll-like receptor (TLR) agonists. In a previous study the glycosylated flavonoid quercetin 3O-sophoroside (Q3OS) was found to co-purify with Bet_v_1 from pollen and reported as a physiological Bet_v_1 ligand.[7] Phytohormones, including phytoprostanes and brassinosteroids, are low-molecular-weight compounds present in pollen extract. 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. We examined how known birch pollen-derived molecules influence the endolysosomal processing of Bet v 1, thereby shaping its allergenicity
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