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

口服牛β-乳球蛋白肽片段诱导的免疫抑制作用

基本信息

批准号：
13660117
负责人：
ENOMOTO Atsushi
金额：
$ 2.3万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13660117/
关键词：
Oral tolerance T cell response Antibody response Epitope Class and subclass Cytokine Peptide Cow's milk allergy 経口寛容牛乳アレルゲンアレルゲン ELISA β-ラクトグロブリン

项目摘要

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.

有充分证据表明，口服蛋白质抗原通常会诱导对随后的肠胃外免疫产生全身免疫反应，这被称为口服耐受。在这项研究中，牛β-乳球蛋白（β-Lg）是最有效的牛奶过敏原之一。选择 91-104 肽作为靶蛋白抗原，每组 5 只雌性 C3H/HeN 小鼠口服 3 mg 合成肽 91-104 或129-143源自β-Lg，在腹腔注射全抗原之前10天，我们检查并比较了在所有喂养的每组小鼠中观察到的免疫耐受的程度和表位特异性。肽已被证明包含天然蛋白的免疫显性T和B细胞决定簇。通常发现口服肽91-104或129-143可以起到作用。与给予 PBS 的对照小鼠相比，用多针肽合成系统对每组汇集的抗血清进行隐式、详细的表位作图研究，将抗 β-Lg 血清抗体的产生降低至约 1/2。本研究中使用的肽片段的口服耐受性可能不针对针对蛋白质抗原上相应表位的抗体反应，但能够优先抑制对与喂养分开的不同决定簇的反应然而，就 T 细胞反应而言，口服肽主要抑制针对肽中抗原决定簇的反应。