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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.

在白塞氏病患者中观察到复发性口腔口疮先于眼部炎症，这表明口腔链球菌在该病的病因学中发挥着作用。热处理的链球菌抗原可诱发白塞氏病患者的眼部炎症或全身症状。此外，在这些患者的血清中检测到了针对视网膜热休克蛋白 60 (HSP60) 的自身抗体的存在。注射提取的视网膜 HSP60 也会在治疗的大鼠中诱发实验性葡萄膜炎。使用分子生物学方法评估视网膜 HSP60 和化脓性链球菌 (S. pyogenes) 的 HSP60 的特征。通过聚合酶链反应从牛视网膜 cDNA 文库和化脓性链球菌 DNA 中分离出编码 HSP60 的基因。确定了HSP60编码区的DNA序列，并根据该DNA序列预测了所编码蛋白质的氨基酸序列。将合成肽(50 nmol)用弗氏完全佐剂乳化并注射到大鼠体内。链球菌和牛视网膜HSP60的氨基酸序列的比较揭示了约200个残基区域，具有47％的同源性。实验性葡萄膜炎主要在接种视网膜HSP60衍生肽或相当于人HSP65残基245-259的链球菌HSP60衍生肽的大鼠中诱导。视网膜和链球菌 HSP60 氨基酸组成被认为对于研究白塞病诱导机制非常重要且有用。