Molecular mechanisms of immune diseases.

这个小组的所有成员都参与了从基因水平上分析免疫功能障碍与疾病之间的关系。从抗体和胸腺细胞到信号转导机制，这个小组研究了与病理病因相关的广泛课题。1)该小组发现了一种不寻常的MHC单倍型与B1细胞的异常增加之间存在联系，B1细胞是分泌B细胞的重要自身免疫抗体。他们还报道，这个新基因被称为imh-1，与位于第4染色体末端的肿瘤坏死因子受体家族紧密相连。此外，该小组还发现，Mott-1基因在Mott细胞中表达，Mott细胞是从B1系细胞分化而来的，存在于免疫疾病和BCLL患者中，与第4染色体上的imh-1基因连锁。2.)该小组报道了B细胞特异性蓝蛋白激酶(BRK)和JAK2激酶可以通过IL5刺激而被激活。该组织还报告了t…IL-5R信号转导通路中存在较多的HAT异常是XID小鼠B细胞对IL-5刺激反应弱的原因。3.)这个团队成功地克隆了编码CD86的基因，CD86是一种发挥T细胞激活共刺激分子功能的分子。通过降低CD28/CD80和CD86信号的表达，可以诱导特异性耐受。在已经表现出异常免疫反应的SLE、类风湿性关节炎和特应性皮炎的动物模型中，他们观察到通过降低CD28/CD80和CD86信号的表达，显著抑制了异常免疫反应。4.)在其对细胞内信号在淋巴细胞激活中的作用的持续研究中，该小组通过培育Lyn激酶和HS1缺陷小鼠，在分子水平上分析了这些分子调节失调的影响。该小组还确定了酪氨酸磷酸化HS1蛋白的结构。5.)这组研究表明，取代抗原肽中的氨基酸会改变对抗原肽的免疫反应。6.)该小组证明了HIV env蛋白gp160可以与CaM结合，产生一种二聚体，由于细胞内钙离子的积累而导致细胞凋亡。此外，该小组还观察到，包膜蛋白GP 120与CD4细胞的结合导致了FasL的产生，并诱导了CD4和CD8细胞的凋亡。较少

All members of this group are involved in the analysis of the relationships between immune dysfunction and disease on a genetic level. From antibodies and thymocytes to signal transduction mechanisms, this group study a wide range of subjects related to pathological causation. 1.) This group discovered the existence of linkage between an unusual MHC haplotype and the abnormal increase in B1 cells, which are important autoimmune antibody secreting B cells. They also reported that the novel gene, which was dubbed Imh-1, is closely linked to the TNF receptor family located on the end of the 4th chromosome. In addition, the group found that the Mott-1 gene, expressed in Mott cells, which are terminally differentiated from B1 lineage cells and present in patients with immune diseases and BCLL,is linked to the Imh-1 locus on the 4th chromosome. 2.) This group reported that B Cell specific bluton kinase (Brk) and JAK2 kinase can be activated via stimulation with IL5. The group also reported t … More hat irregularities in the IL-5R signal transduction pathway are responsible for the weak response of B cells to IL-5 stimulation in XID mice. 3.) This group was successful in cloning the gene which encodes CD86, a molecule which functions as a costimulatory molecule for T cell activation. By decreasing CD28/CD80 and CD86 signal expression, specific tolerance can be induced. In animal models of SLE,rheumatoid arthritis and atopic dermatitis which already show abnormal immune reactivity, they observed a significant suppression of the abnormal immune reactivity by decreasing CD28/CD80 and CD86 signal expression. 4.) In its continued investigation of the role of intracellular signaling in the activation of lymphocytes, this group, by developing Lyn kinase and HS1 deficient mice, analyzed the effects of dysregulation of these molecules on a molecular level. The group also determined the structure of tyrosine phosphory lated HS1 protein. 5.) This group showed that substitution of amino acids in sntigenic peptides altered the immune response to the antigenic peptides. 6.) This group demonstrated that HIV env protein gp 160 can bind to CaM,producing a dimmer that causes apoptosis due to intracellular accumulation of Ca2+. Furthermore, this group observed that binding of the env protein gp 120 to CD4 cells causes FasL production and an induction of apoptosis in CD4 and CD8 cells. Less