Regulation of ectopic expression of HLA class II genes.

HLA II 类基因异位表达的调节。

• 批准号: 01480192
• 负责人: KIMURA Akinori
• 金额: $ 4.35万
• 依托单位: Medical Institute of Bioregulation, Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480192/
• 关键词: HLA; Polymorphisms; Promoter region; Expression; Transcription factor; 発現調節; TNF; IFN; トランスジェニックマウス; DNAタイピング; 自己免疫疾患; HLAクラスII遺伝子; 転写調節; サイトカイン; 核蛋白

To decipher the molecular mechanism of the association between HLA and autoinsune diseases, we have investigated the polymorphisms of HLA class I and class 11 genes in the coding and promoter regions. The highly polymorphic second exons of HLA-B. DRB1. DRBS, DRB4. DRB5. DRB6. DQA1. DQB1. DPAI. and DPBI genes were analyzed by the PCR-SSOP and PCR-SSCP methods. and 27, 51, 3.1.4.3.9.14.8. and 36 alleles. respectively. were defined. In addition, cytoplasmic exons of HLA-DRA and DQBL genes were found to be polymorphic, as well 9 allelic differences in the promoter region of the DQAL gene were identified. These polymorphisms were analysed in healthy individuals antipatients with several autoimmune diseases including IDDM. RA, Graves' disease. Behcet's disease, Takayasu arteritis, Hashim to hyroiditis. SLE. mixed connective tissue disease, and specific alleles were identified to be strongly associated with each disease. Moreover, the regulation of the HLA class 11 genes, especially their inductions by cytokinesis such as interferons and TNFs were investigated in detail. and it was found that the HLA-DQAL gene was differently regulated from the other class 11 genes by means of expressivity and inducibility via a DQAL gene-specific positive transcription factor NF-TRS. The binding sites of NF-TRS is overlapping with that of another transcription factor NF-Y and the polymorphism at the sites was found to affect the binding affinity for these factors. suggesting that the expression of the HLA-DQAL gene is allele-specific and may play a role in immune regulation and in developing the autoimmune diseases.

为了解解HLA与自动疾病疾病之间关联的分子机制，我们研究了编码和启动子区域中HLA I类和11类基因的多态性。 HLA-B的高度多态性第二外显子。 DRB1。 DRB，DRB4。 DRB5。 DRB6。 DQA1。 DQB1。 DPAI。通过PCR-SSOP和PCR-SSCP方法分析了DPBI基因。和27、51、3.1.4.3.9.14.8。和36个等位基因。分别。被定义。此外，发现HLA-DRA和DQBL基因的细胞质外显子是多态性的，并且发现了DQAL基因启动子区域的9个等位基因差异。这些多态性在患有多种自身免疫性疾病（包括IDDM）的健康个体抗癌体中进行了分析。 RA，Graves病。 Behcet氏病，高山动脉炎，哈希姆到杂炎。 sle。混合结缔组织疾病和特定等位基因与每种疾病密切相关。此外，详细研究了HLA 11类基因的调节，尤其是细胞因子诱导的诱导。发现HLA-DQAL基因通过DQAL基因特异性阳性转录因子NF-TRS的表现性和诱导性与其他11类基因不同。 NF-TR的结合位点与另一个转录因子NF-Y的结合位点重叠，并且发现位点的多态性会影响这些因素的结合亲和力。表明HLA-DQAL基因的表达是特定于等位基因的，并且可能在免疫调节和发展自身免疫性疾病中发挥作用。

项目成果

Kimura, A., Sasazuki, T.: "Epitope analysis of workshop panels : combined study of oligotyping and serological typing" "HLA 1991 Vol. I". Oxford University Press.

Kimura, A., Sasazuki, T.：“研讨会小组的表位分析：寡分型和血清学分型的联合研究”“HLA 1991 Vol. I”。

Sasazuki, T., Urabe, K., Harada, F., Iwanaga, T., Kimura, A.: "Structural analysis of the genes within the HLA class III region on chromosome 6." New aspects of the genetics of molecular evolution (Kimura, M., and Takahara, N. EDS.). Academic Press. (1991

Sasazuki, T.、Urabe, K.、Harada, F.、Iwanaga, T.、Kimura, A.：“6 号染色体 HLA III 类区域内基因的结构分析。”

Fukui,Y.,Esaki,Y.,Yasunami,M.,Kimura,K.,Hirokawa,K.,Nishimura,Y.,Sasazuki,T.: "T cell repertoire and selfーtolerance in the transgenic mice with HLAーDRA on X chromosome.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford,

Fukui, Y.、Esaki, Y.、Yasunami, M.、Kimura, K.、Hirokawa, K.、Nishimura, Y.、Sasazuki, T.：“HLA-转基因小鼠的 T 细胞库和自身耐受性X 染色体上的 DRA。载于“HLA 1991 Vol.II”eds.Sasazuki,T.,Aizawa,M.,Tsuji,K.”牛津大学出版社，牛津，

Sasazuki,T.et al: "HLA-linked immune suppression in humans" Immunology,Supplement. 2. 21-24 (1989)

Sasazuki,T.et al：“人类 HLA 相关免疫抑制”免疫学，补充。

Tsuchiya,K.,Kondo,M.,Kimura,A.,Nishimura,Y.,and Sasazuki,T.: "DRB1 and/or DQB1 locus control susceptibility and DRB1 controls resistance to RA.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)

Tsuchiya,K.、Kondo,M.、Kimura,A.、Nishimura,Y. 和 Sasazuki,T.：“HLA 1991 Vol.II 中的 DRB1 和/或 DQB1 位点控制易感性，DRB1 控制对 RA 的耐药性”