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.
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.


CONCLUSIONS
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.
Junior Research Group 1 Experimental Allergology, Paul-Ehrlich-Institut, Paul Ehrlich St 59, Langen 63225, Germany. todma@pei.de
Anne
A
Ilchmann
Sven
S
Burgdorf
Stephan
S
Scheurer
Zoe
Z
Waibler
Ryoji
R
Nagai
Anne
A
Wellner
Yasuhiko
Y
Yamamoto
Hiroshi
H
Yamamoto
Thomas
T
Henle
Christian
C
Kurts
Ulrich
U
Kalinke
Stefan
S
Vieths
Masako
M
Toda
D000485:Allergens / Q000276:immunology / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005512:Food Hypersensitivity / Q000276:immunology / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D015416:Maillard Reaction; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000485:Allergens; D017127:Glycation End Products, Advanced; D051117:Scavenger Receptors, Class A; D010047:Ovalbumin