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Evaluation of the sensitizing potential of food proteins using two mouse models

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Author: Smit, J. · Zeeuw-Brouwer, M.L.D. · Roest, M. van · Jong, G. de · Bilsen, J. van
Type:article
Date:2016
Source:Toxicology Letters, 262, 62-69
Identifier: 573059
doi: DOI:10.1016/j.toxlet.2016.09.005
Keywords: Biology · Allergenic proteins · Allergenicity · Dendritic cells · Food allergy · Mouse models · Sensitization · T cells · Biomedical Innovation · Healthy Living · Life · RAPID - Risk Analysis for Products in Development · ELSS - Earth, Life and Social Sciences

Abstract

The current methodology to identify allergenic food proteins is effective in identifying those that are likely to cross-react with known allergens. However, most assays show false positive results for low/non-allergens. Therefore, an ex vivo/in vitro DC-T cell assay and an in vivo mouse model were used to distinguish known allergenic food proteins (Ara h 1, β-Lactoglobulin, Pan b 1, bovine serum albumin, whey protein isolate) from low/non allergenic food proteins (soy lipoxygenase, gelatin, beef tropomyosin, rubisco, Sola t 1). CD4+ T cells from protein/alum-immunized mice were incubated with corresponding protein-pulsed bone marrow-derived DC and analyzed for cytokine release. All known allergens induced Th2 responses in vitro, whereas soy lipoxygenase, gelatin or beef tropomyosin did not. Sola t 1 and rubisco induced a more generalized T cell response due to endotoxin contamination, indicating the endotoxin-sensitivity of the DC-T assay. To analyze responses in vivo, mice were orally sensitized on days 0 and 7. Known allergens induced IgE and mMCP-1 release upon oral challenge at day 16, whereas the low/non-allergens did not. Both the DC-T cell assay and the mouse model were able to distinguish 5 known allergens from 5 low/non-allergens and may be useful to identify novel allergenic food proteins. © 2016 Elsevier Ireland Ltd