Malgorzata Teodorowicz1, Hannah E Zenker2, Arifa Ewaz1, Theodoros Tsallis1, Andreas Mauser3, Sabrina Gensberger-Reigl3, Nicolette W de Jong4, Kasper A Hettinga2, Harry J Wichers5, R J Joost van Neerven1,6, Huub F J Savelkoul1. 1. Cell Biology & Immunology, Wageningen University & Research Centre, Wageningen, the Netherlands. 2. Food Quality & Design Group, Wageningen University & Research Centre, Wageningen, the Netherlands. 3. Food Chemistry, Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany. 4. Internal Medicine, Allergology & Clinical Immunology, Erasmus University Medical Centre Rotterdam, the Netherlands. 5. Food & Biobased Research, Wageningen University & Research Centre, Wageningen, the Netherlands. 6. Friesland Campina, Amersfoort, the Netherlands.
Abstract
SCOPE: β-lactoglobulin (BLG) is a major cow milk allergen encountered by the immune system of infants fed with milk-based formulas. To determine the effect of processing on immunogenicity of BLG, this article characterized how heated and glycated BLG are recognized and internalized by APCs. Also, the effect of heat-induced structural changes as well as gastrointestinal digestion on immunogenicity of BLG is evaluated. METHODS AND RESULTS: The binding and uptake of BLG from raw cow milk and heated either alone (BLG-H) or with lactose/glucose (BLG-Lac and BLG-Glu) to the receptors present on APCs are analyzed by ELISA and cell-binding assays. Heated and glycated BLG is internalized via galectin-3 (Gal-3)and scavenger receptors (CD36 and SR-AI) while binding to the receptor for advanced glycation end products (R AGE) does not cause internalization. Receptor affinity of BLG is dependent on increased hydrophobicity, β-sheet exposure and aggregation. Digested glycated BLG maintained binding to sRAGE and Gal-3 but not to CD36 and SR-AI, and is detected on the surface of APCs. This suggests a mechanism via which digested glycated BLG may trigger innate (via RAGE) and adaptive immunity (via Gal-3). CONCLUSIONS: This study defines structural characteristics of heated and glycated BLG determining its interaction with APCs via specific receptors thus revealing enhanced immunogenicity of glycated versus heated BLG.
SCOPE: β-lactoglobulin (BLG) is a major cow milk allergen encountered by the immune system of infants fed with milk-based formulas. To determine the effect of processing on immunogenicity of BLG, this article characterized how heated and glycated BLG are recognized and internalized by APCs. Also, the effect of heat-induced structural changes as well as gastrointestinal digestion on immunogenicity of BLG is evaluated. METHODS AND RESULTS: The binding and uptake of BLG from raw cow milk and heated either alone (BLG-H) or with lactose/glucose (BLG-Lac and BLG-Glu) to the receptors present on APCs are analyzed by ELISA and cell-binding assays. Heated and glycated BLG is internalized via galectin-3 (Gal-3)and scavenger receptors (CD36 and SR-AI) while binding to the receptor for advanced glycation end products (R AGE) does not cause internalization. Receptor affinity of BLG is dependent on increased hydrophobicity, β-sheet exposure and aggregation. Digested glycated BLG maintained binding to sRAGE and Gal-3 but not to CD36 and SR-AI, and is detected on the surface of APCs. This suggests a mechanism via which digested glycated BLG may trigger innate (via RAGE) and adaptive immunity (via Gal-3). CONCLUSIONS: This study defines structural characteristics of heated and glycated BLG determining its interaction with APCs via specific receptors thus revealing enhanced immunogenicity of glycated versus heated BLG.
Authors: Sebastian A Jensen; Alessandro Fiocchi; Ton Baars; Galateja Jordakieva; Anna Nowak-Wegrzyn; Isabella Pali-Schöll; Stefano Passanisi; Christina L Pranger; Franziska Roth-Walter; Kristiina Takkinen; Amal H Assa'ad; Carina Venter; Erika Jensen-Jarolim Journal: World Allergy Organ J Date: 2022-09-15 Impact factor: 5.516