The analysis of HLA-linked immune suppression genes and their expression.

为了研究人类免疫调节的遗传控制，我们已经使用天然抗原进行了群体研究和家族研究，以证明免疫抑制基因（Is基因）的存在。在本研究中，分析HLA连锁的Is基因的表达在天然抗原，如链球菌细胞壁抗原（SCW），日本血吸虫抗原（Sj），柳杉花粉抗原（CP）和麻风杆菌抗原（ML）在体外的免疫反应，我们进行了封闭实验，使用各种抗HLA单克隆抗体（mAb）。当以SCW、Sj和ML作为攻击抗原时，T_4辅助性T细胞的增殖反应被抗HLA-DR单抗完全阻断。相反，无反应，这是通过T8抑制性T细胞的IS基因控制的，被转换为高反应的抗DQ单克隆抗体在培养物中。因此，我们认为HLA-DR是免疫应答基因的产物，HLA-DQ是免疫应答基因的产物。 ...更多信息 自我是存在基因的产物。由于Dw 2和Dw 12单倍型在对SCW或Sj的免疫应答表型上不同，因此将<beta>从本文建立的cDNA克隆推导的Dw 12的DQw 1-链的氨基酸序列与Dw 2的DQw 1进行比较<beta>，以确定诱导抗原特异性抑制的特异性表位。1结构域的高变区<beta>被认为是负责这些单倍型之间的免疫抑制的功能差异。在体外CP特异性IgE产生系统和体外T淋巴细胞增殖反应中也清楚地证明了抗原特异性T8抑制性T细胞。遗传学、细胞免疫学和分子生物学清楚地证明了人类免疫反应的遗传控制。HLA类<II>分子在免疫应答和免疫抑制中起重要作用的发现为人类免疫调节和疾病易感性的机制提供了线索。少

To investigate the genetic control of immune regulation in humans, we have already performed the population study and family study to demonstrate the existence of immune suppression genes(Is-genes), using natural antigens. In the present study, to analyse the expression of HLA-linked Is-genes in the immune response to natural antigens, such as streptococcal cell wall antigen(SCW), schistosoma japonicum antigen(Sj), cryptomeria pollen antigen(CP) and mycobacterium leprae antigen(ML) in vitro, we performed blocking experiments using various anti HLA monoclonal antibodies(mAbs). When we use SCW, Sj and ML, as challenging antigens, the proliferative response of T4 helper T cells was completely blocked by anti HLA-DR mAb. On the contrary, nonresponse, which is controlled by Is-genes through T8 suppressor T cells, was converted to high response by the addition of anti DQ mAb in the culture. Therefore, we concluded that the HLA-DR was the product of immune response gene and that the HLA-DQ it … More self was the product of Is-genes. Because Dw2 and Dw12 haplotypes were different in their phenotype of immune responsiveness to SCW or Sj, amino acid sequence of DQwl <beta> -chain of Dw12 deduced from cDNA clone established here was compared with that of DQwl <beta> of Dw2 to determine the specific epitope to induce antigen specific suppression. The hypervariable region of <beta> 1 domain was considered to be responsible for the functional difference in the immune suppression between these haplotypes. Antigen specific T8 suppressor T cells were also clearly demonstrated in CP specific IgE production system in vitro and T lymphoproliferative response to ML in vitro.The genetic control of immune response in humans was clearly demonstrated using genetics, cellular immunology, and molecular biology. Our findings that HLA-class <II> molecules played major role in the immune response and suppression do provide a clue as to the mechanism of immune regulation and disease susceptibility in humans. Less