TY - JOUR
T1 - Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity
T2 - Role of macrophage scavenger receptor class A type I and II
AU - Ilchmann, Anne
AU - Burgdorf, Sven
AU - Scheurer, Stephan
AU - Waibler, Zoe
AU - Nagai, Ryoji
AU - Wellner, Anne
AU - Yamamoto, Yasuhiko
AU - Yamamoto, Hiroshi
AU - Henle, Thomas
AU - Kurts, Christian
AU - Kalinke, Ulrich
AU - Vieths, Stefan
AU - Toda, Masako
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Food allergy
KW - Maillard reaction
KW - T-cell immunogenicity
KW - dendritic cells
KW - food allergen
KW - macrophage scavenger receptor
UR - http://www.scopus.com/inward/record.url?scp=73149101622&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73149101622&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2009.08.013
DO - 10.1016/j.jaci.2009.08.013
M3 - Article
C2 - 19864011
AN - SCOPUS:73149101622
VL - 125
SP - 175-183.e11
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 1-3
ER -