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Investigation for Autoreactive T-cell to Autoantigen in Behcet's Disease

白塞氏病自身反应性 T 细胞对自身抗原的研究

基本信息

批准号：
10671658
负责人：
TANAKA Takao
金额：
$ 1.54万
依托单位：
Tokyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

The observation of recurrent oral aphtha preceding ocular inflammation in patients with Behcet's disease suggests a role of oral Streptococcus in the etiology of this disease. Heat-treated Streptoccus antigen can induce ocular inflammation or systemic symptoms in Behcet's disease patients. Furthermore, the presence of an autoantibody against retinat heat-shock protein 60 (HSP60) has been detected in the sera of these patients. Injection of extracted retinal HSP60 also induces experimental uveitis in treated rats. The characteristics of retinal HSP60 and HSP60 from Streptoccus pyogenes (S. pyogenes) were evaluated using a molecular biological approach. The gene encoding HSP60 was isolated by polymerase chain reaction from a bovine retinal cDNA library and from S. pyogenes DNA. The DNA sequence of the HSP60 coding region was determined, and the amino acid sequences of the encoded proteins were predicted from the DNA sequence. The synthetic peptide (50 nmol) was emulsified with Freund's complete adjuvant and injected into rats. Comparison of the amino acid sequences of Streptococcal and bovine retinal HSP60 revealed about 200 residue region with 47% homology. Experimental uveitis was mainly induced in rats inoculated with retinal HSP60-derived peptide or Streptococcus HSP60-derived peptide that is equivalent to residues 245-259 of human HSP65. Retinal and Streptococcal HSP60 amino acid composition are thought to be important and useful for investigating the mechanisms involved in the induction of Behcet's disease.

白塞病患者在眼部炎症之前反复出现口腔口疮的观察表明口腔链球菌在这种疾病的病因学中起作用。热处理链球菌抗原可在白塞病患者中诱导眼部炎症或全身症状。此外，已在这些患者的血清中检测到针对视网膜热休克蛋白60（HSP 60）的自身抗体的存在。注射提取的视网膜HSP 60也诱导治疗大鼠的实验性葡萄膜炎。视网膜HSP 60和化脓性链球菌HSP 60的特性。化脓性链球菌）进行评价。通过聚合酶链反应从牛视网膜cDNA文库和S.化脓菌DNA。测定了HSP 60编码区的DNA序列，并从DNA序列预测了编码蛋白的氨基酸序列。将合成肽（50 nmol）用弗氏完全佐剂乳化并注射到大鼠中。与牛视网膜HSP 60的氨基酸序列比较，发现约200个氨基酸残基，同源性为47%。实验性葡萄膜炎主要在接种视网膜HSP 60衍生肽或链球菌HSP 60衍生肽（其相当于人HSP 65的残基245-259）的大鼠中诱导。视网膜和链球菌HSP 60的氨基酸组成被认为是重要的和有用的研究参与诱导白塞氏病的机制。