Regulation of ectopic expression of HLA class II genes.

为了阐明人类白细胞抗原与自身免疫性疾病相关的分子机制，我们研究了人类白细胞抗原I类和11类基因在编码区和启动子区域的多态性。人类白细胞抗原B基因第二外显子高度多态。DRB1.DRBS、DRB4。DRB5.DRB6.DQA1。DQB1。DPAI。用聚合酶链式反应-单链构象多态和聚合酶链式反应-单链构象多态方法分析DPBI基因。和27，51，3.1.4.3.9.14.8。36个等位基因。分别进行了分析。都被定义为。此外，DQAL基因启动子区存在9个等位基因差异，发现了DQAL基因的9个等位基因。对患有包括IDDM在内的几种自身免疫性疾病的健康人进行了这些基因多态性的分析。RA，格雷夫斯病。白塞病、大动脉炎、结肠炎。SLE。混合性结缔组织病，特异性等位基因被鉴定为与每种疾病密切相关。此外，还详细研究了人类白细胞抗原11类基因的调控，特别是干扰素和肿瘤坏死因子等胞质因子对其的诱导作用。研究发现，HLADQAL基因通过DQAL基因特异的正转录因子NF-TRS的表达和诱导性不同于其他11类基因的表达调控。核转录因子受体的结合位点与另一转录因子核因子-Y的结合位点重叠，并发现其多态影响这些因子的结合亲和力。提示HLADQAL基因的表达具有等位基因特异性，可能在免疫调节和自身免疫性疾病的发生发展中发挥作用。

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.