Immunosuppressive effects induced by oral administration of peptide fragments derived from bovine β -lactoglobulin

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It has been well documented that oral administration of protein antigens commonly induces systemic immunological unresponsiveness to the subsequent parenteral immunization which is termed oral tolerance. In this study, bovine β -lactoglobulin ( β -Lg), one of the most potent cow's milk allergens, was selected as a target protein antigen, and groups of 5 female C3H/HeN mice were orally given with 3 mg of synthetic peptides 91-104 or 129-143 derived from β -Lg 5 times during 10 days prior to intraperitoneal injections with the whole antigen. Using this experimental system. we examined and compared the magnitude and epitope specificity of immunological tolerance observed in each group of the mice. All the feeding peptides have been shown to include both the immunodominant T and B cell determinants of the native protein. The oral administration of the peptides 91-104 or 129-143 was usually found to lower the production of anti- β -Lg serum antibody to approximately 1/2, as compared with the PBS-administrated control mice. Interestingly, detailed epitope-mapping study of antisera pooled for each group with the multi-pin peptide synthesis system indicates that the oral tolerance with the peptide fragments used in this study may not be directed to the antibody response against the corresponding epitopes on the protein antigen, but be capable of preferentially inhibiting the response to distinct determinants which are separate from the feeding peptides. In the case of T cell response, the orally given peptides, however, could mainly suppress the response against the antigenic determinant located in the peptides.