title: Effects of glycation of the model food allergen ovalbumin on antigen uptake and presentation by human dendritic cells.
abstract: Advanced glycation endproducts (AGEs) of food proteins resulting from the Maillard reaction after cooking or heating may have particular importance in food allergy. The underlying immunological mechanisms are only poorly understood. The aim of the study was to examine the effects of AGE derived from the model food allergen ovalbumin (AGE-OVA) on dendritic cells (DCs), their immunostimulatory capacity and the T-cell response compared with regular OVA. For this purpose, human immature DCs were exposed to fluorescein isothiocyanate (FITC)-labelled AGE-OVA and FITC-labelled regular OVA and uptake was analysed by flow cytometry and fluorescence microscopy. Furthermore, autologous CD4(+) T-cell proliferation and cytokine production induced by mature DCs loaded with AGE-OVA were compared with those induced by mature DCs loaded with OVA. Finally, expression of the receptor for advanced glycation endproducts (RAGE) and activation of the transcription factor nuclear factor (NF)-kappaB by AGE were investigated. Internalization of FITC-AGE-OVA by immature DCs was significantly increased compared with FITC-OVA. Blocking the mannose receptor, macropinocytosis or the scavenger receptor strongly reduced uptake of both FITC-OVA and FITC-AGE-OVA. In a comparison of CD4(+) T cells co-cultured with AGE-OVA-loaded mature DCs versus those co-cultured with OVA-loaded mature DCs, AGE-OVA DCs were found to produce more interleukin (IL)-6 and to induce a stronger T helper type 2 (Th2) and a weaker Th1 cytokine response, while there was no difference in proliferation of CD4(+) T cells. The expression of RAGE was higher on immature DCs compared with mature DCs. AGE-OVA-exposed immature DCs showed a stronger expression of RAGE and activation of the transcription factor NF-kappaB compared with OVA-loaded immature DCs. Our data indicate that AGE-OVA may be more immunogenic/allergenic than regular OVA.
authors.affiliation: Department of Dermatology, University of Mainz, Mainz, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Hilmenyuk
authors.forename: Iris
authors.initials: I
authors.lastname: Bellinghausen
authors.forename: Bärbel
authors.initials: B
authors.lastname: Heydenreich
authors.forename: Anne
authors.initials: A
authors.lastname: Ilchmann
authors.forename: Masako
authors.initials: M
authors.lastname: Toda
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
authors.forename: Joachim
authors.initials: J
authors.lastname: Saloga
mesh_terms: D000485:Allergens / Q000276:immunology / Q000378:metabolism; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology*; D005512:Food Hypersensitivity / Q000276:immunology*; D017127:Glycation End Products, Advanced / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D010047:Ovalbumin / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000485:Allergens; D000906:Antibodies; D016207:Cytokines; D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051996:Transcription Factor RelA; D010047:Ovalbumin