Food allergy is on the rise, and preventive/therapeutic procedures are needed. We explored a preventive protocol for milk allergy with the oral administration of a Gly-m-Bd-30K soy-derived peptide that contains cross-reactive epitopes with bovine caseins. B/T-cross-reactive epitopes were mapped using milk-specific human sera and monoclonal antibodies on overlapping and recombinant peptides of Gly-m-Bd-30K by SPOT and cell proliferation assays. Bioinformatics tools were used to characterize epitopes on the 3D-modelled molecule, and to predict the binding to HLA alleles. The peptide was orally administrated to mice that were then IgE-sensitized to milk proteins. Immunodominant B-epitopes were mainly located on the surface of the Nt-fragment. The use of a soy-peptide-containing an immunodominant cross-reactive T-epitope, along with a single B epitope, prevents IgE-mediated milk sensitization through the induction of Th1-mediated immunity and induction of blocking IgG. The use of a safe soy-peptide may represent a promising alternative for preventing milk allergy.

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