Molecular mechanism in Sjogren's syndrome

干燥综合征的分子机制

• 批准号: 11470123
• 负责人: SUMIDA Takayuki
• 金额: $ 9.28万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470123/
• 关键词: Sjogren's syndrome; Tcell receptor; T cell epitope; g-amylase; analogpeptide; シェーグレン症候群

The purpose of the present study is to clarify the mechanism in the generation of Sjogren's syndrome (SS), T cell receptor (TCR) genes in T cells infiltrating in labial salivary glands, lacrymal glands, and interstitium of kidneys have been analyzed by molecular biology technology. The results showed thatT cells in organs recognized antigens in the context of HLA molecule, suggesting the antigen-driven stimulation. Moreover, the antigens for T cells in salivary glands have been examined by several methodsatthe level ofamino acids. We have obtained the following two findings. 1) Salivary type a-amylase function as gland-specific autoantigen recognized by T cells in the salivary glands. 2) One of T'cell epitopes of T cells in salivary glands is NPFRPWWERYQPV (AA68-80) of a-amylase. In near future, autoreactive T cells might be induced into anergy by the vaccination of analog peptides of a-amylase, resulting in the regulation of SS in the antigen-specific fashion.

本研究旨在阐明干燥综合征(SS)的发病机制，应用分子生物学技术对渗入唇涎腺、泪腺和肾间质的T细胞的T细胞受体(TCR)基因进行分析。结果表明，器官中的T细胞是在人类白细胞抗原分子的背景下识别抗原的，提示为抗原驱动的刺激。此外，还用几种氨基酸水平的方法检测了唾液腺T细胞的抗原。我们得到了以下两个发现。1)唾液型α-淀粉酶是唾液腺中T细胞识别的腺特异性自身抗原。2)唾液腺T细胞的T细胞表位之一是α-淀粉酶的NPFRPWWERYQPV(AA68-80)。在不久的将来，免疫α-淀粉酶的模拟多肽可以诱导自身反应性T细胞进入无能状态，从而以抗原特异性的方式调节SS。

项目成果

Akimoto, T., et al.: "Anti-prothrombin autoantibodies in severe preedampsia and abortion"Am.J.Med.. 110. 188-191 (2001)

Akimoto, T., et al.：“抗凝血酶原自身抗体在严重先兆流产和流产中的应用”Am.J.Med.. 110. 188-191 (2001)

Kojo,S., et al.: "Dysfunction of TCR AV24AJ18+BV11+double negative regulatory NKT cells in autoimmune diseases."Arthritis Rheum.. (in press).

Kojo,S. 等人：“自身免疫性疾病中 TCR AV24AJ18 BV11 双阴性调节 NKT 细胞的功能障碍。”关节炎大黄..（出版中）。

Murata, H., et al.: "Quantitative analysis offetal michirochimerism in Japanese women with systemic sclerosis"Mod.Rheumatol. 11. 259-260 (2001)

Murata, H. 等人：“日本系统性硬化症女性胎儿微嵌合现象的定量分析”Mod.Rheumatol。

Matsumoto,I,. Et. Al.: "α-amylase function as salevary glands-specific self T cell epitopes in patients with Sjogren's syndrome."int. J. Mol. Med.. 3. 485-490 (1999)

Matsumoto, I,.等人：“α-淀粉酶在干燥综合征患者中发挥着唾液腺特异性自身 T 细胞表位的作用。”J. Mol. 3. 485-490 (1999)

Keino,H., et al.: "Identification of regulatory T cells among in vivo expanded ocular T cells in mice with experimental autoimmune uveoretinitis."Clin.Exp.Immunol.. (in press).

Keino, H. 等人：“实验性自身免疫性葡萄膜视网膜炎小鼠体内扩增的眼部 T 细胞中调节性 T 细胞的鉴定。”Clin.Exp.Immunol..（出版中）。