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，我们已经进行了群体研究和家系研究，利用自然抗原证明了免疫抑制基因(IS-基因)的存在。在本研究中，我们用不同的抗人类白细胞抗原的单抗(MAbbs)进行了体外阻断实验，以分析在天然抗原如链球菌细胞壁抗原(SCW)、日本血吸虫抗原(Sj)、隐孢子虫花粉抗原(Cp)和麻风杆菌抗原(ML)的免疫应答中，与人类白细胞抗原相关的IS基因的表达。当我们用SCW、Sj和ML作为攻击抗原时，T4辅助性T细胞的增殖反应被抗HLA-DR单抗完全阻断。相反，在培养中加入抗DQ单抗后，由IS-基因通过T8抑制T细胞控制的无应答转变为高应答。因此，我们认为人类白细胞抗原DR是免疫应答基因的产物，人类白细胞抗原DQ是…。更多的自我是IS基因的产物。由于DW2和DW12单倍型对SCW或Sj的免疫应答表型不同，因此，从本研究建立的克隆中推导出的DW12的DQwl；β&gt；链氨基酸序列与DW2的DQwl&lt；β&gt；的氨基酸序列进行比较，以确定诱导抗原特异性抑制的特异性表位。~lt；β&gt；1结构域的高变区被认为是导致这些单倍型之间免疫抑制功能差异的原因。在体外CP特异性IgE产生系统和体外对ML的T淋巴细胞增殖反应中，也清楚地显示了抗原特异性的T8抑制T细胞。从遗传学、细胞免疫学和分子生物学的角度，清楚地证明了人类免疫反应的遗传控制。我们的研究发现，人类白细胞抗原类分子在免疫反应和抑制中发挥了主要作用，这确实为人类免疫调节和疾病易感性的机制提供了线索。较少

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