IMMUNOGENETIC STUDIES OF COLLAGEN ARTHRITIS

II型胶原诱导性关节炎（CIA）是一种实验诱导的， 慢性外周关节炎的遗传控制的自身免疫模型。 涉及多个基因。 一个近交系大鼠群体， 耐药、同源、原型和重组大鼠品系被用于 阐明CIA的几个参数，直接关系到关节 风湿性疾病患者的炎症。 1)一种基因的存在 关节炎和自身免疫性疾病易感性之间的相关性 对CIA易感性的比较应变分析 和其他关节炎的实验模型。 2)以确定是否存在差异 在CIA易感性的差异有关的特异性， 对II型胶原的免疫应答，来自抗性和 正在分析敏感菌株的相对反应性（通过ELISA 与大鼠胶原蛋白（II）的分离的螺旋溴化氰（CB）肽。 3)RT 1单倍型的菌株是低应答者和CIA抗性的。 RT 1内重组体将用于鉴定RT 1亚区， 控制抗胶原免疫反应。 检测胶原蛋白特异性 T-抑制细胞，非致关节炎佐剂将在 次免疫 4)存在特定的“致关节炎”区域， 胶原分子被提出，并将在两种方法中进行测试： 用生物化学制备的单独CB肽免疫， 异源II型胶原; B）使用杂交瘤技术制备 一组与大鼠胶原蛋白（II）反应的单克隆抗体， 测试被动地将关节炎转移到未免疫大鼠的能力。 5)组织培养技术正在被用来研究相互作用 滑膜细胞，胶原蛋白和免疫T细胞的作用，重点是 干扰素和白细胞介素。 易感者之间的遗传差异 和抗性大鼠，在生产或响应这些 免疫调节剂将受到质疑。

Type II collagen-induced arthritis (CIA) is an experimentally induced and genetically controlled autoimmune model of chronic, peripheral arthritis. Multiple genes are involved. An inbred rat colony of susceptible and resistant, congenic, prototype and recombinant rat strains is being used to elucidate several parameters of CIA that directly relate to joint inflammation in rheumatic disease patients. 1) The existence of a genetic relatedness between susceptibility to arthritis and to autoimmune diseases is being questioned by comparative strain analysis of susceptibility to CIA and other experimental models of arthritis. 2) To determine if differences in susceptibility to CIA are related to differences in specificity of the immune response to type II collagen, antisera from resistant and susceptible strains are being analyzed (by ELISA) for relative reactivity with isolated helical cyanogen-bromide (CB) peptides of rat collagen (II). 3) Strains of the RT1 haplotype are low responders and CIA-resistant. Intra-RT1 recombinants will be used to identify the RT1 subregion that controls anti-collagen immune reactivity. To test for collagen-specific T-suppressor cells, non-arthritogenic adjuvants will be used during immunization. 4) The existence of specific "arthritogenic" regions of the collagen molecule is proposed and will be tested in two approaches: a) immunization with individual CB peptides prepared biochemically from heterologous type II collagens; b) use of hybridoma technology to prepare a panel of monoclonal antibodies reactive with rat collagen (II) which will be tested for ability to passively transfer arthritis to unimmunized rats. 5) Tissue culture techniques are being used to investigate the interaction of synovial cells, collagen, and immune T-cells with emphasis on the roles of interferon and interleukins. Genetic differences between susceptible and resistant rats, in the production of or response to these immunomodulators will be questioned.