| Popis: |
The Maillard reaction is a non-enzymatic reaction between reducing sugars and compounds with free amino groups like proteins and takes place during thermal processing of foods. The reaction leads to modification of proteins with various glycation structures such as Nε-(carboxymethyl-)lysine (CML), methylglyoxal (MGO)-induced hydroimidazolones and pyrraline. These modifications have an influence on the immunogenic and allergenic properties of food allergens, e.g. glycation enhances the CD4+ T-cell immunogenicity of the egg white allergen ovalbumin (OVA). In this study, distinct glycation structures contributing to the enhanced T-cell immunogenicity of crude glycated OVA (AGE-OVA) should be identified. For this purpose OVA was selectively modified with several glycation structures such as CML and pyrraline. T-cell immunogenicity of glycated OVA samples was assessed using a co-culture system of murine bone marrow-derived dendritic cells (BMDCs) and Ova-specific CD4+ T-cells. Incubation of the cells with OVA modified with pyrraline (Pyr-OVA), but none of the other selectively modified samples, resulted in enhanced CD4+ T-cell activation and cytokine production by the T-cells. This enhanced T-cell immunogenicity of Pyr-OVA is mediated by DCs, although Pyr-OVA and other glycated OVAs did not affect BMDC maturation. However, Pyr-OVA was highly taken up by BMDCs compared to native OVA and other glycated OVAs. Deficiency of scavenger receptor class A (SR-A), but not inhibition of galectin-3 or class B scavenger receptors, in BMDCs reduced the uptake of Pyr-OVA. CD4+ T-cell activation by Pyr-OVA was also reduced when SR-A-/- BMDCs were used in the co-culture system. The allergenicity of Pyr-OVA was assessed using a mouse model of food allergy and mice sensitized with Pyr-OVA had higher IgE levels and showed stronger clinical symptoms than mice sensitized with native OVA. Pyrraline-modified food allergens could be taken up more efficiently by DCs, via binding of the glycation structure to SR-A, and in turn enhance CD4+ T-cell immunogenicity of the allergens. Since CD4+ T-cells play a critical role to induce IgE production by B-cells pyrraline-modification might be capable to enhance the allergic potential of food allergens. This study will help to get a better understanding of molecular mechanisms of food allergies. |
