Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity: Role of macrophage scavenger receptor class A type I and II

• Published in: Journal of allergy and clinical immunology 2010, Vol.125 (1), p.175-183.e11
• Main Authors: Ilchmann, Anne, BSc, Burgdorf, Sven, PhD, Scheurer, Stephan, PhD, Waibler, Zoe, PhD, Nagai, Ryoji, PhD, Wellner, Anne, BSc, Yamamoto, Yasuhiko, MD, PhD, Yamamoto, Hiroshi, MD, PhD, Henle, Thomas, PhD, Kurts, Christian, MD, Kalinke, Ulrich, PhD, Vieths, Stefan, PhD, Toda, Masako, PhD
• Format: Article
• Language: English
• Subjects: Allergens - immunology; Allergens - metabolism; Allergic diseases; Allergies; Allergy and Immunology; Animals; Antigen Presentation; Biological and medical sciences; Bone marrow; Bone Marrow Cells; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Coculture Techniques; dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Digestive allergic diseases; food allergen; Food allergies; Food allergy; Food Hypersensitivity - immunology; Food Hypersensitivity - physiopathology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glycation End Products, Advanced - immunology; Glycation End Products, Advanced - metabolism; Immunopathology; Lymphocyte Activation; macrophage scavenger receptor; Maillard Reaction; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin - immunology; Ovalbumin - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Scavenger Receptors, Class A - metabolism; T cell receptors; T-cell immunogenicity; T-Lymphocytes - cytology; T-Lymphocytes - immunology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2009.08.013

Background The Maillard reaction occurs between reducing sugars and proteins during thermal processing of foods. It produces chemically glycated proteins termed advanced glycation end products (AGEs). The glycation structures of AGEs are suggested to function as pathogenesis-related immune epitopes in food allergy. Objective This study aimed at defining the T-cell immunogenicity of food AGEs by using ovalbumin (OVA) as a model allergen. Methods AGE-OVA was prepared by means of thermal processing of OVA in the presence of glucose. Activation of OVA-specific CD4+ T cells by AGE-OVA was evaluated in cocultures with bone marrow–derived murine myeloid dendritic cells (mDCs) as antigen-presenting cells. The uptake mechanisms of mDCs for AGE-OVA were investigated by using inhibitors of putative cell-surface receptors for AGEs, as well as mDCs deficient for these receptors. Results Compared with the controls (native OVA and OVA thermally processed without glucose), AGE-OVA enhanced the activation of OVA-specific CD4+ T cells on coculture with mDCs, indicating that the glycation of OVA enhanced the T-cell immunogenicity of the allergen. The mDC uptake of AGE-OVA was significantly higher than that of the controls. We identified scavenger receptor class A type I and II (SR-AI/II) as a mediator of the AGE-OVA uptake, whereas the receptor for AGEs and galectin-3 were not responsible. Importantly, the activation of OVA-specific CD4+ T cells by AGE-OVA was attenuated on coculture with SR-AI/II–deficient mDCs. Conclusion SR-AI/II targets AGE-OVA to the MHC class II loading pathway in mDCs, leading to an enhanced CD4+ T-cell activation. The Maillard reaction might thus play an important role in the T-cell immunogenicity of food allergens.