TY - JOUR
T1 - Enhanced Uptake of Processed Bovine β-Lactoglobulin by Antigen Presenting Cells
T2 - Identification of Receptors and Implications for Allergenicity
AU - Teodorowicz, Malgorzata
AU - Zenker, Hannah E.
AU - Ewaz, Arifa
AU - Tsallis, Theodoros
AU - Mauser, Andreas
AU - Gensberger-Reigl, Sabrina
AU - de Jong, Nicolette W.
AU - Hettinga, Kasper A.
AU - Wichers, Harry J.
AU - van Neerven, R. J.Joost
AU - Savelkoul, Huub F.J.
N1 - Funding Information:
This work is part of the research programme iAGE/TTW with project number 14536, which is (partly) financed by the Netherlands Organisation for Scientific Research (NWO).
Publisher Copyright:
© 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85102288866&partnerID=8YFLogxK
U2 - 10.1002/mnfr.202000834
DO - 10.1002/mnfr.202000834
M3 - Article
C2 - 33559978
AN - SCOPUS:85102288866
SN - 1613-4125
VL - 65
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 8
M1 - 2000834
ER -