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

已经充分证明，口服蛋白抗原通常诱导对随后的胃肠外免疫的全身免疫无应答性，这被称为口服耐受。在这项研究中，牛β -乳球蛋白（β -Lg），最有效的牛奶过敏原之一，被选为目标蛋白抗原，和5组雌性C3 H/HeN小鼠口服3毫克的合成肽91-104或129-143来自β -Lg 5次在10天内腹腔注射前的整个抗原。使用这个实验系统。我们检查并比较了在每组小鼠中观察到的免疫耐受的大小和表位特异性。所有的摄食肽已被证明包括天然蛋白质的免疫显性T和B细胞决定簇。经口给予肽91-104或129-143通常发现使抗- β -Lg血清抗体的产生降低至PBS给药对照小鼠的约1/2。有趣的是，用多针肽合成系统对每组合并的抗血清进行的详细表位作图研究表明，本研究中使用的肽片段的口服耐受性可能不针对蛋白质抗原上相应表位的抗体应答，但能够优先抑制对与摄食肽分离的不同决定簇的应答。然而，在T细胞应答的情况下，口服给予的肽主要抑制针对位于肽中的抗原决定簇的应答。

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.