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ANALYSIS OF CLASS II MHC DERIVED ANTIGENIC PEPTIDES FROM HUMAN INTESTINE

人肠 II 类 MHC 衍生抗原肽的分析

基本信息

批准号：
09670565
负责人：
OSHITANI Nobuhide
金额：
$ 1.98万
依托单位：
THIRD DEPARTMENT OF INTERNAL MEDICINE, OSAKA CITY UNIVERSITY MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670565/
关键词：
CLASS II MHC HLA-DR ANTIGENIC PEPTIDE CROHN'S DISEASE ULCERATIVE COLITIS TANDEM-MASS ANALYSIS MASS ANALYSIS HCADR class II MHC HLA-DR 炎症性腸疾患 HLA DR

项目摘要

The specific antigen responsible for the pathogenesis of inflammatory bowel disease is unknown. We isolated HLA-DR-associated peptides from human intestine and sequenced their amino-acid residues by ion-trap tandem mass spectrometry equipped with online reverse-phase high performance liquid chromatography. Serum antibody titers against two of the above determined antigens were measured. We detected 73 parent proteins from 4 controls, 10 patients with ulcerative colitis, and 10 patients with Crohn's disease. The calculated molecular masses (m/z) of these peptides ranged from 582.2 to 2988.5, representing 7 to 27 amino acid residues. Sixty-eight of these 73 parent proteins were exogenous proteins. Neither MHC nor invariant chain-derived peptides were found among human intestinal class II MHC-associated peptides, contrary to previous findings for transformed cells. Escherichia coli-, Saccharomyces cerevisiae-, and Caenorhabditis elegans-derived peptides were found veryfrequently in patients with inflammatory bowel disease. Serum antibody titers against S.cerevisiae and C.elegans were measured, and were significantly higher in patients with inflammatory bowel disease than in controls. The present results suggest that in vivo antigen processing by antigen-presenting cells and T lymphocytes in human intestine are participated with exogenous antigen presentation. Increased immune responses against S.cerevisiae and C.elegans were found in patients with inflammatory bowel and may participate as dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.

负责炎症性肠病发病机制的特异性抗原尚不清楚。我们从人类肠道中分离出HLA-DR相关肽，并通过配备在线反相高效液相色谱的离子阱串联质谱法对其氨基酸残基进行测序。测量针对上述确定的抗原中的两种的血清抗体滴度。我们检测了73个亲本蛋白，从4个对照组，10例溃疡性结肠炎，10例克罗恩病。这些肽的计算分子量（m/z）范围为582.2至2988.5，代表7至27个氨基酸残基。这73个亲本蛋白中有68个是外源蛋白。无论是MHC还是不变链衍生的肽被发现在人类肠道II类MHC相关肽，与以前的研究结果转化细胞。大肠杆菌、酿酒酵母和秀丽隐杆线虫源性肽在炎症性肠病患者中非常常见。测定了血清中抗酿酒酵母和秀丽隐杆线虫的抗体滴度，炎症性肠病患者的抗体滴度显著高于对照组。本研究结果表明，在体内抗原呈递细胞和T淋巴细胞的抗原加工参与外源性抗原呈递。在炎症性肠病患者中发现对酿酒酵母和秀丽隐杆线虫的免疫应答增加，并且可能作为对肠道植物群的免疫应答失调参与炎症性肠病的发病机制。