Journal Article

Cross-Linking of β-Lactoglobulin Enhances Allergic Sensitization Through Changes in Cellular Uptake and Processing

Marija Stojadinovic, Raymond Pieters, Joost Smit and Tanja Cirkovic Velickovic

in Toxicological Sciences

Volume 140, issue 1, pages 224-235
Published in print July 2014 | ISSN: 1096-6080
Published online April 2014 | e-ISSN: 1096-0929 | DOI:
Cross-Linking of β-Lactoglobulin Enhances Allergic Sensitization Through Changes in Cellular Uptake and Processing

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  • Medical Toxicology
  • Food Microbiology


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Cross-linking of proteins has been exploited by the food industry to change food texture and functionality but the effects of these manipulations on food allergenicity still remain unclear. To model the safety assessment of these food biopolymers, we created cross-linked bovine β-lactoglobulin (CL-BLG) by laccase treatment. The purpose of the present study was to compare the immunogenicity and allergenicity of CL-BLG with native BLG in a mouse model of food allergy. First, BALB/c mice were intragastrically sensitized and orally challenged with BLG or CL-BLG and BLG-specific serum antibodies and splenic leukocyte cytokine production and cell proliferation were measured. Hereafter, epithelial protein uptake was monitored in vitro and in vivo and the effects of BLG cross-linking on interactions with dendritic cells were analyzed in vitro. Sensitization of mice with CL-BLG resulted in higher levels of IgE, IgG1, and IgG2a. In contrast, a subsequent oral challenge with CL-BLG resulted in lower mast cell degranulation. Cross-linking of BLG reduced its epithelial uptake but promoted sampling through Peyer's patches. Differences in endocytosis by dendritic cells (DCs) and in vitro endolysosomal processing were observed between BLG and CL-BLG. CL-BLG primed DCs induced higher Th2 response in vitro. Cross-linking of BLG increased its sensitizing capacity, implying that the assessment of highly polymerized food proteins is of clinical importance in food allergy. Moreover, manufacturers of foods or therapeutic proteins should pay considerate attention to the health risk of protein aggregation.

Keywords: protein cross-linking; protein aggregation; food processing; allergic sensitization; β-lactoglobulin; mouse model of food allergy

Journal Article.  5431 words.  Illustrated.

Subjects: Medical Toxicology ; Food Microbiology

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