T CELL RECEPTOR V GENES IN COLLAGEN INDUCED ARTHRITIS

胶原蛋白诱发关节炎中的 T 细胞受体 V 基因

• 批准号: 3457470
• 负责人: Tariq M Haqqi
• 金额: $ 9.7万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-15 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3457470
• 关键词: T cell receptor; chronic disease /disorder; collagen; collagen disorder; diagnosis design /evaluation; disease /disorder model; genetic strain; genotype; haploidy; immunogenetics; immunoglobulin G; immunotherapy; inflammation; laboratory mouse; model design /development; rheumatoid arthritis

DESCRIPTION (adapted from investigator's abstract and/or aims): The arthritis which develops in susceptible strains of mice immunized with either heterologous or autologous type II collagen has many similarities with human rheumatoid arthritis. These similarities include synovial pannus, joint edema and swelling, infiltration by lymphocytes, autoimmune reactions to type II collagen, formation of IgG (rheumatoid factor) which are MHC linked. Although susceptibility to this animal model of arthritis is clearly dependent on MHC genes, additional roles for non-MHC genes, in determining susceptibility, have been suggested by observations on the SWR mouse strain. This strain of mice has the H-2q MHC haplotype normally susceptible to the induction of CIA. It has since been shown that resistance to the development of the induction of CIA is correlated with the deletion of T cell receptor genes in H-2q mice. These observations, including the study of other types of T cell receptor deletions, indicate that there is a restrictive usage of T cell receptor V-beta genes in determining susceptibility to CIA. It is suggested that the deletion mutants are resistant to CIA because they cannot develop arthritogenic T cells and T cell dependent antibodies directed against epitopes on type II collagen in the joint. The applicant proposes to define the T cell population in arthritic joints in this model, i.e., is it oligoclonal or polyclonal, identify and sequence the specific T cell receptors within the joint and then develop an immunotherapy based on synthetic peptides corresponding to the disease associated T cell receptor V-beta gene sequences. The long-term goal is directed at experimental prevention and/or reversal of CIA in this animal model.

描述（改编自研究者的摘要和/或目标）： 关节炎是在免疫小鼠的易感品系中发生的 无论是异源还是自体 II 型胶原蛋白都有许多相似之处 与人类类风湿性关节炎。 这些相似之处包括滑液 血管翳、关节水肿肿胀、淋巴细胞浸润、自身免疫 对 II 型胶原蛋白的反应，形成 IgG（类风湿因子） MHC 相关。 尽管对这种关节炎动物模型的易感性已明确 依赖于 MHC 基因，非 MHC 基因的额外作用，在决定 易感性，已通过对 SWR 小鼠的观察得出 拉紧。 该品系小鼠通常具有 H-2q MHC 单倍型 容易受到 CIA 的诱导。 此后的事实表明 对 CIA 诱导发展的抵抗力与 H-2q 小鼠中 T 细胞受体基因的缺失。 这些观察结果， 包括对其他类型 T 细胞受体缺失的研究，表明 T 细胞受体 V-β 基因的使用受到限制 确定对 CIA 的敏感性。 建议删除 突变体对 CIA 有抵抗力，因为它们不能发展出致关节炎的 T 针对 II 型表位的细胞和 T 细胞依赖性抗体 关节中的胶原蛋白。 申请人提议定义T细胞 该模型中关节炎关节的群体，即它是寡克隆还是 多克隆，识别并测序特定 T 细胞受体 联合开发基于合成肽的免疫疗法 对应于疾病相关T细胞受体V-beta基因 序列。 长期目标是实验性预防 和/或在该动物模型中 CIA 的逆转。