HLA DR4 TRANSGENIC MICE/ARTHRITIS MODEL

描述：（改编自申请人的摘要）- RA是一种自身免疫性 在西欧和美国，这种疾病的患病率为1%， 其他种族的频率不同。 遗传易感性 RA的发生与人类免疫反应基因HLA-DR 4有关。 这 联想被认为部分是由于不受控制的激活 通过来自滑膜的自身抗原蛋白分子检测的CD 4 + T细胞 接头. 这项提议建议使用HLA-DR trg小鼠来开发一种新的治疗方法。 基于肽的免疫调节治疗， 这个过程 HLA-DRB*0401和 *0405 trg小鼠，均与RA易感性相关， 将用于确定人免疫原性肽表位 自身抗原性蛋白质，通过产生抗原特异性T细胞杂交瘤， 用人类蛋白质免疫这些小鼠。 两个这样的人体关节 蛋白质，人II型胶原蛋白（hCII），滑膜的主要成分， 人软骨细胞糖蛋白39（HCgp 39）可以诱导 *0401 trg小鼠的关节炎。 40%的RA患者的T细胞可以 对HCgp 39的反应。 HLA-DR 4 trg小鼠模型可能是一个重要的 用于测试用于RA的新的基于肽的免疫调节治疗的体内模型 患者 这些肽可以用于开发狭窄的抗原特异性免疫原。 通过诱导无反应性或Th 1/Th 2偏移来产生耐受性，这会更好 患者耐受性比我们认为的通常非常毒性的类风湿关节炎治疗更好， 知没有

DESCRIPTION: (Adapted from the applicant's abstract) - RA is an autoimmune disease with a prevalence of 1% in western Europe and America, but with a variable frequency in other ethnic groups. The genetic susceptibility to develop RA is associated with the human immune response genes HLA-DR4. This association is thought to be due in part to an uncontrolled activation of CD4+ T cells by autoantigenic protein molecules derived from synovial joints. This proposal suggests using HLA-DR trg mice to develop a peptide-based immunomodulatory treatment aiming specifically at controlling this process. HLA-DRB*0401 and *0405 trg mice, both associated with susceptibility to RA, would be used to determine the immunogenic peptide epitopes of human autoantigenic proteins by producing antigen-specific T cell hybridomas after immunization of these mice with the human proteins. Two such human joint proteins, human collagen type II (hCII), a major constituent of synovial cartilage, and human chondrocyte glycoprotein 39 (HCgp39) can induce arthritis in the *0401 trg mouse. Forty percent of RA patients' T cells can respond to HCgp39. The HLA-DR4 trg mouse model could be an important in vivo model for testing new peptide-based immunomodulatory treatments for RA patients. Such peptides could be used to develop a narrow antigen-specific tolerance by inducing anergy or Th1/Th2 skewing, which would be much better tolerated by patients than the often very toxic treatments for RA that we know of.