Oshitani Nobuhide, Hato Fumihiko, Kitagawa Seiichi, Maeda Kiyoshi, Higuchi Kazuhide, Matsumoto Takayuki, Arakawa Tetsuo
Department of Gastroenterology, Osaka City University Medical School, Osaka, Japan.
Int J Mol Med. 2003 Jan;11(1):99-104.
Isolation of antigenic peptides from the MHC-groove has contributed to the understanding of T cell responses. However, these MHC-associated peptides have been isolated from various murine and human cell lines. The specific antigen responsible for the pathogenesis of inflammatory bowel disease is unknown. We examined antigenic peptides bound to the class II major histocompatibility complex (MHC) groove in human intestine by ion-trap tandem mass spectrometry equipped with online reverse-phase high performance liquid chromatography. We detected 55 parent proteins from 4 controls, 9 patients with ulcerative colitis, and 9 patients with Crohn's disease. The calculated molecular masses (m/z) of these peptides ranged from 874.4 to 2727.4, representing 10-26 amino acid residues. Fifty-one of these 55 parent proteins were exogenous proteins. Escherichia coli-, Saccharomyces cerevisiae-, and Caenorhabditis elegans-derived peptides were found frequently in patients with inflammatory bowel disease. The present results suggest that in vivo antigen processing by antigen-presenting cells and T lymphocytes in human intestine participate with exogenous antigen presentation. Increased immune responses against E. coli, S. cerevisiae and C. elegans found in patients with inflammatory bowel may participate as dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.
从MHC凹槽中分离抗原肽有助于理解T细胞反应。然而，这些与MHC相关的肽是从各种小鼠和人类细胞系中分离出来的。导致炎症性肠病发病机制的特定抗原尚不清楚。我们通过配备在线反相高效液相色谱的离子阱串联质谱法检测了人肠道中与II类主要组织相容性复合体（MHC）凹槽结合的抗原肽。我们从4名对照、9名溃疡性结肠炎患者和9名克罗恩病患者中检测到了55种母体蛋白。这些肽的计算分子量（m/z）范围为874.4至2727.4，代表10 - 26个氨基酸残基。这55种母体蛋白中有51种是外源蛋白。在炎症性肠病患者中经常发现源自大肠杆菌、酿酒酵母和秀丽隐杆线虫的肽。目前的结果表明，人肠道中抗原呈递细胞和T淋巴细胞的体内抗原加工参与了外源抗原呈递。在炎症性肠病患者中发现的针对大肠杆菌、酿酒酵母和秀丽隐杆线虫的免疫反应增强，可能作为对肠道菌群的失调免疫反应参与炎症性肠病的发病机制。
