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

Received 14 March 2009; received in revised form 6 July 2009; accepted 11 August 2009. published online 28 October 2009.

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.

Key words: Food allergy, food allergen, Maillard reaction, T-cell immunogenicity, dendritic cells, macrophage scavenger receptor

a Junior Research Group 1 “Experimental Allergology,”, Paul-Ehrlich-Institut, Langen, Germany

d Junior Research Group 2 “Novel vaccination strategies and early immune responses,” Paul-Ehrlich-Institut, Langen, Germany

c Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany

b Institute for Molecular Medicine and Experimental Immunology, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany

e Department of Food and Nutrition, Laboratory of Biochemistry & Nutritional Science, Japan Women's University, Tokyo, Japan

f Institute of Food Chemistry, Technische Universität Dresden, Dresden, Germany

g Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

h TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany

Reprint requests: Masako Toda, PhD, Junior Research Group 1 “Experimental Allergology,” Paul-Ehrlich-Institut, Paul Ehrlich St 59, Langen 63225, Germany.

Supported in part by Paul-Ehrlich-Institut and Deutsche Forschungsgemeinschaft (DFG Vi 165/6)

Disclosure of potential conflict of interest: S. Burgdorf has received research support from the German Research Foundation. S. Vieths is an Associate of the Institute for Product Quality, Berlin; has received honoraria from Phadia, Uppsala, Sweden, and the Food Allergy Resource and Research Program, United States; is a consultant for MARS Chocolate UK Ltd; has received research support from the European Union (EuroPrevall), the German Research Foundation, the Research Fund of the German Food Industry, Monsanto Company, Pioneer Hi-Bred International, the Food Allergy Research & Resource Program, and the European Directorate for the Quality of Medicines and Health Care (EDQM); is an Executive Committee Member of the European Academy of Allergy and Clinical Immunology; is Chairman of the Allergen Standardization Subcommittee and Secretary of the Allergen Nomenclatures Subcommittee of the International Union of Immunological Societies (IUIS); is a Registered Expert with the European Agency for the Evaluation of Medicinal Products (EMEA) and the European Pharmacopoeia Commission; is Chairman of Technical Committee 275 of the European Committee for Standardization (CEN); and is a Member of the Food Allergy Working Group for the German Society for Allergy and Clinical Immunology. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(09)01250-0

doi:10.1016/j.jaci.2009.08.013

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