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Laboratory | Immune system | Allergies
We are currently studying a population of patients allergic to goat's milk without associated cow's milk allergy. Despite sequence identities ranging from 87% to 91% between caprine and bovine caseins, these patients possess IgE antibodies that bind specifically to the caprine caseins without recognizing the bovine ones. Using complementary approaches, i.e. controlled enzymatic hydrolysis and production of recombinant fusion proteins, we demonstrated that, for these patients, the allergenicity of the caprine β-casein could be abolished by substituting five amino acids residues.
Allergenicity of food proteins has been correlated to their structural conformation and their resistance to proteolysis. In peanut, the 2S albumins Ara h 2 and Ara h 6 are the most potent allergens. We showed that heating of 2S albumins in solution induced their denaturation and their aggregation and thereby reduced significantly the IgE-binding capacity and the elicitation potency (FP7 Europrevall program). Complete denaturation of Ara h 6 induced by chemical reduction and alkylation also abolished the IgE-binding capacity. Moreover, 2S-albumins contain a protease resistant core which retains most of the allergenicity after digestion. The trypsin resistance of Ara h 6 and the allergenicity of the digestion products were abolished after selective disruption of 2 out 5 disulfide bonds. A correct folding of Ara h 6 is then required for its proteolysis resistance and its elicitation potency. In contrast to Ara h 6, chemical denaturation of Ara h 2 did not fully suppress the allergenic potency. This is due to the presence of an immunodominant linear IgE-binding epitope that contains hydroxyprolines. We demonstrated that these post-translational modifications are required for an optimal IgE-binding to Ara h 2. The absence of hydroxyproline could then affect the accuracy of component-resolved diagnostics using recombinant Ara h 2.
In addition to the impact of heating processes on the allergenicity of purified Ara h 1, 2 and 6, we demonstrated that inclusion of peanut flour in fat-rich matrices decreased the IgE-binding capacity of peanut allergens, probably by limiting their bioaccessibility. However, the allergenicity of in vitro peanut digesta was increasing with longer digestion time, thus suggesting the progressive release of potent allergenic molecules following the disruption of the food matrix. These results are in line with oral food challenges performed with peanut allergic patients showing that objective symptoms occurred at higher doses after inclusion in fat-rich matrices, but were also more severe, thus underlying the complex role of food matrices in peanut food allergy. The bioaccessibility and the biodisponibility of allergens in different food matrices are now investigated within the frame of the European Program iFAAM.
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