LSIT

描述：(改编自申请人的摘要)-血清阴性 脊柱关节病是一组炎症性疾病，其中 脊柱、周围关节、皮肤、眼睛和身体的其他组织可以是 牵涉其中。人类白细胞抗原B27在以下几种疾病中有很强的关联性 这些疾病。在大多数情况下，疾病发生在胃肠道之后。 感染几种肠道细菌中的一种。申请者 已经成功地引发了自发性炎症性关节炎 缺乏内源性小鼠的人类白细胞抗原-B27转基因小鼠的指甲变化 β-2微球蛋白。这种疾病主要在雄鼠身上发现。 他们的研究表明，这种疾病是由游离的HLA-B27 Heavy介导的 细胞表面的链条。在这项提案中，他们将完全 通过对这些小鼠的自发性疾病的描述 免疫遗传解剖。首先，他们将确认 通过研究其他I类分子在疾病过程中的作用 转基因小鼠。接下来，他们将确定I班的潜在角色 在疾病过程中使用II类分子 敲除(Abo)基因。接下来，他们将确定CD4T细胞的作用 在疾病过程中通过引入CD4基因敲除和 将CD8敲除基因导入他们的B27转基因小鼠。最终的遗传学研究 以确定转运蛋白基因(TAP)、蛋白酶体 (LMP)和T细胞受体重排(RAG)基因在其中起作用 疾病。他们将确定I类、II类、CD4和CD8T的作用 抗体对处于起始期和效应期的细胞 在疾病开始之前和之后的启动研究 疾病的发病。在第二组实验中，他们将尝试 确定导致触发的内源性/环境抗原 通过从B27分子中洗脱多肽并将其与 它们与来自无病原体群体中的小鼠的那些相同。他们会试着 给无病原体B27小鼠注射 具有B27结合基序的肠杆菌多肽。在这个项目的最终目标中 提案，他们将确定胶原蛋白是否是 疾病的发病机制。他们预计，这些研究将打开新的局面。 对人类脊椎关节病免疫遗传学的洞察。

DESCRIPTION: (Adapted from the applicant's abstract) - Seronegative spondyloarthropathies are a group of inflammatory disease in which the spine, peripheral joints, skin, eyes, and other tissues of the body may be involved. There is a strong association of the HLA-B27 antigen in several of the diseases. In most cases, the disease occurs after gastrointestinal infection with one of several species of enterobacteria. The applicants have been successful in generating spontaneous inflammatory arthritis and nail changes in their HLA-B27 transgenic mice lacking endogenous mouse beta-2 microglobulin. The disease is primarily found in the male mice. Their studies suggest that the disease is mediated by free HLA-B27 heavy chains on the cell surface. In this proposal, they will completely characterize the spontaneous disease in these mice by a through immunogenetic dissection. First of all, they will confirm the specificity of the B27 molecule in the disease process by studying other class I transgenic mice. Next, they will determine the potential role of class I versus class II molecules in this disease process by using a class II knock-out (Abo) gene. Next, they will determine the role of CD4 T cells versus CD8 T cells in the disease process by introducing CD4 knock-out and CD8 knock-out genes into their B27 transgenic mice. The final genetic study would be done to determine whether transporter genes (Tap), proteasome (Lmp), and T cell receptor rearrangement (Rag) genes play a role in this disease. They will determine the role of class I, class II, CD4, and CD8 T cells in the initiation phase versus the effector phase by antibody initiation studies prior to the initiation of the disease and after the onset of the disease. In the second set of experiments, they will try to identify the endogenous/environmental antigen which causes the triggering of the disease by eluting the peptides from the B27 molecules and comparing them with those from the mice in the pathogen-free colony. They will try to induce the disease in the pathogen-free B27 mice by injecting them with enterobacterial peptides with B27 binding motifs. In the final aim of this proposal, they will determine whether collagen is a target in the pathogenesis of the disease. These studies, they expect, will open up new insights into the immunogenetics of human spondyloarthropathy.