LSIT

描述：（改编自申请人摘要）-血清阴性 脊椎关节病是一组炎性疾病， 脊柱、外周关节、皮肤、眼睛和身体的其它组织可以 涉案 HLA-B27抗原在几种疾病中有很强的相关性。 疾病。 在大多数情况下，该疾病发生在胃肠道后 几种肠杆菌中的一种感染。 申请人 已经成功地产生了自发性炎症性关节炎， 缺乏内源性HLA-B27转基因小鼠的指甲变化 β 2微球蛋白 这种疾病主要在雄性小鼠中发现。 他们的研究表明，这种疾病是由游离的HLA-B27重链介导的。 在细胞表面的链。 在这份提案中，他们将完全 通过一个贯穿于这些小鼠的自发性疾病的特征， 免疫遗传解剖 首先他们会确认 B27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类的潜在作用 与II类分子相比， 敲除（Abo）基因。 下一步，他们将确定CD 4 T细胞的作用， 通过引入CD 4敲除， CD 8敲除基因植入B27转基因小鼠。 最后的基因研究 将做，以确定是否转运基因（Tap），蛋白酶体 (Lmp)T细胞受体重排（Rag）基因在这一过程中发挥作用。 疾病 它们将决定I类、II类、CD 4和CD 8 T细胞的作用。 通过抗体观察处于起始期与效应期的细胞 在疾病开始之前和之后的启动研究 疾病的发作。 在第二组实验中，他们将尝试 识别引起以下触发的内源性/环境抗原 通过从B27分子中洗脱肽并比较 将它们与无病原体群体中的小鼠进行比较。 他们将试图 在无病原体的B27小鼠中通过注射 具有B27结合基序的肠细菌肽。 在这个最终的目标 建议，他们将确定胶原蛋白是否是一个目标， 疾病的发病机制。 这些研究，他们希望，将开辟新的 人类脊柱关节病免疫遗传学的见解。

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.