Glycation of the Major Milk Allergen β‐Lactoglobulin Changes Its Allergenicity by Alterations in Cellular Uptake and Degradation

• Published in: Molecular nutrition & food research 2018-09, Vol.62 (17), p.e1800341-n/a
• Main Authors: Perusko, Marija, Roest, Manon, Stanic‐Vucinic, Dragana, Simons, Peter J., Pieters, Raymond H. H., Cirkovic Velickovic, Tanja, Smit, Joost J.
• Format: Article
• Language: English
• Subjects: Allergenicity; Allergens; Allergens - chemistry; Allergens - immunology; Allergens - pharmacokinetics; Allergies; Animals; Bone marrow; Caco-2 Cells; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cytokines; Cytokines - metabolism; Degradation; Degranulation; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Endocytosis; Endocytosis - drug effects; Endocytosis - physiology; Enzyme-linked immunosorbent assay; Female; Flow cytometry; Food; food allergens; Food allergies; Food Handling; Food processing; Glycosylation; Humans; Immune system; Immunogenicity; Immunoglobulin E; Intestine; Lactoglobulin; Lactoglobulins - chemistry; Lactoglobulins - immunology; Lactoglobulins - pharmacokinetics; Lymphocytes T; Lysosomes - drug effects; Lysosomes - metabolism; Maillard Reaction; Mice, Inbred C3H; Milk - chemistry; Milk - immunology; Milk Hypersensitivity - immunology; Proteins; uptake and degradation by DCs; β-Lactoglobulin
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201800341

Scope During food processing, the Maillard reaction (МR) may occur, resulting in the formation of glycated proteins. Glycated proteins are of particular importance in food allergies because glycation may influence interactions with the immune system. This study compared native and extensively glycated milk allergen β‐lactoglobulin (BLG), in their interactions with cells crucially involved in allergy. Methods and results BLG was glycated in MR and characterized. Native and glycated BLG were tested in experiments of epithelial transport, uptake and degradation by DCs, T‐cell cytokine responses, and basophil cell degranulation using ELISA and flow cytometry. Glycation of BLG induced partial unfolding and reduced its intestinal epithelial transfer over a Caco‐2 monolayer. Uptake of glycated BLG by bone marrow–derived dendritic cells (BMDC) was increased, although both BLG forms entered BMDC via the same mechanism, receptor‐mediated endocytosis. Once inside the BMDC, glycated BLG was degraded faster, which might have led to observed lower cytokine production in BMDC/CD4+ T‐cells coculture. Finally, glycated BLG was less efficient in induction of degranulation of BLG‐specific IgE sensitized basophil cells. Conclusions This study suggests that glycation of BLG by MR significantly alters its fate in processes involved in immunogenicity and allergenicity, pointing out the importance of food processing in food allergy. The Glycation of food allergens resulting from Maillard reaction may influence processes involved in the sensitizing and eliciting phase during allergy. Native and glycated milk allergen β‐lactoglobulin are compared for epithelial transport, uptake and degradation by DCs, T‐cell cytokine responses, and basophil activation. Results suggest that glycation of β‐lactoglobulin influence its interactions with cells involved in the initiation and elicitation of allergic immune responses.