Title (eng)

Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity

Author

Andreas Regner   University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna

Franziska Roth-Walter   University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna

Karin Hufnagl   University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna

Erika Jensen-Jarolim   University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna

Zdenek Dvorak   Palacky University

Gerlinde Hofstetter   University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna

Frank A Redegeld   Utrecht University

Bart R Blokhuis   Utrecht University

Luis F Paciosis   Universidad Politécnica de Madrid

Aila Fakhimahmadi   University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna

Markus Wiederstein   University of Salzburg

Nathalie Szepannek   University of Veterinary Medicine, Vienna / Medical University Vienna / University of Vienna

Publishing

MDPI

Description (eng)

Bet v 1 is the major allergen in birch pollen to which up to 95% of patients sensitized to birch respond. As a member of the pathogenesis-related PR 10 family, its natural function is implicated in plant defense, with a member of the PR10 family being reported to be upregulated under iron deficiency. As such, we assessed the function of Bet v 1 to sequester iron and its immunomodulatory properties on human immune cells. Binding of Bet v 1 to iron quercetin complexes FeQ2 was determined in docking calculations and by spectroscopy. Serum IgE-binding to Bet v 1 with (holoBet v1) and without ligands (apoBet v 1) were assessed by ELISA, blocking experiments and Western Blot. Crosslinking-capacity of apo/holoBet v 1 were assessed on human mast cells and Arylhydrocarbon receptor (AhR) activation with the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for labile iron and phenotypic changes by flow cytometry. Bet v 1 bound to FeQ2 strongly with calculated Kd values of 1 nm surpassing affinities to quercetin alone nearly by a factor of 1000. Binding to FeQ2 masked IgE epitopes and decreased IgE binding up to 80% and impaired degranulation of sensitized human mast cells. Bet v 1 facilitated the shuttling of quercetin, which activated the anti-inflammatory AhR pathway and increased the labile iron pool of human monocytic cells. The increase of labile iron was associated with an anti-inflammatory phenotype in CD14+monocytes and downregulation of HLADR. To summarize, we reveal for the first time that FeQ2 binding reduces the allergenicity of Bet v 1 due to ligand masking, but also actively contributes anti-inflammatory stimuli to human monocytes, thereby fostering tolerance. Nourishing immune cells with complex iron may thus represent a promising antigen-independent immunotherapeutic approach to improve efficacy in allergen immunotherapy.

Object languages

English

Date

2023

Rights

This work is licensed under a
CC BY 4.0 - Creative Commons Attribution 4.0 International License.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Classification

Salicylic-Acid; Receptor; Activation; Protein; Deficiency; Ige; Inhibition; Flavonoids; Mechanism; Immunity

Member of the Collection(s) (1)