Regulation of ectopic expression of HLA class II genes.

为了揭示HLA与自身免疫性疾病相关的分子机制，我们研究了HLA I类和11类基因在编码区和启动子区的多态性。高度多态性的HLA-B第二外显子。DRB1。DRBS DRB4。DRB5。DRB6。DQA1。DQB1。DPAI。采用PCR-SSOP和PCR-SSCP方法对DPBI基因进行分析。27、51、3.1.4.3.9.14.8。36个等位基因。分别。被定义。此外，HLA-DRA和DQBL基因胞质外显子存在多态性，DQAL基因启动子区存在9个等位基因差异。这些多态性在包括IDDM在内的几种自身免疫性疾病的健康个体中进行了分析。格雷夫斯病。白塞氏病，高须动脉炎，哈希姆至水疱炎。系统性红斑狼疮。混合结缔组织疾病和特定等位基因被确定与每种疾病密切相关。此外，还详细研究了HLA 11类基因的调控，特别是干扰素和tnf等细胞因子对其的诱导作用。发现HLA-DQAL基因通过DQAL基因特异性阳性转录因子NF-TRS的表达性和诱导性受到不同于其他11类基因的调控。NF-TRS的结合位点与另一个转录因子NF-Y的结合位点重叠，这些位点的多态性影响了这些因子的结合亲和力。提示HLA-DQAL基因的表达是等位基因特异性的，可能在免疫调节和自身免疫性疾病的发生中发挥作用。

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.