Ovalbumin modified with pyrraline, a Maillard reaction product, shows enhanced T-cell immunogenicity [Immunology]

February 6th, 2014 by Heilmann, M., Wellner, A., Gadermaier, G., Ilchmann, A., Briza, P., Krause, M., Nagai, R., Burgdorf, S., Scheurer, S., Vieths, S., Henle, T., Toda, M.

The Maillard reaction (MR: also referred to as glycation) takes place between reducing sugars and compounds with free amino groups during thermal processing of foods. In the final stage of the complex reaction cascade, the so-called advanced glycation end products (AGEs) are formed, including proteins with various glycation structures. It has been suggested that some AGEs could have immunostimulatory effects. Here, we aimed to identify specific glycation structure(s) that could influence the T-cell immunogenicity and potential allergenicity of food allergens, using ovalbumin (OVA, an egg white allergen) as a model allergen. OVA was specifically modified with representative glycation structures: Nε carboxymethyl lysine (CM-OVA), Nε carboxyethyl lysine (CE-OVA), pyrraline (Pyr-OVA), or methylglyoxal-derived arginine derivatives (MGO-OVA). As well as AGE-OVA, a crude glycation product in thermal incubation of OVA with glucose, only Pyr OVA, but not other modified OVAs, was efficiently taken up by bone marrow-derived murine dendritic cells (BMDCs). The uptake of Pyr OVA was reduced in scavenger receptor class A (SR A)-deficient BMDCs, but not in cells treated with inhibitors of scavenger receptor class B, galectin-3, or blocking antibodies against CD36, suggesting that pyrraline binds to SR-A. Compared to other modified OVAs, Pyr-OVA induced higher activation of OVA-specific CD4+ T-cells in co-culture with BMDCs. Furthermore, compared to native OVA, AGE-OVA and Pyr OVA induced higher IgE production in mice. Pyrraline could induce better allergen uptake by DCs via association with SR A, and subsequently enhance CD4+ T-cell activation and IgE production. Our findings help us to understand how MR enhances the potential allergenicity of food allergens.