HLA DR4 TRANSGENIC MICE/ARTHRITIS MODEL

描述：(改编自申请者的摘要)--RA是一种自身免疫性疾病 疾病在西欧和美洲的流行率为1%，但 在其他民族中频率可变。遗传病的易感性 类风湿关节炎的发生与人类免疫反应基因HLA-DR4有关。这 联想被认为部分是由于不受控制的激活 滑膜自身抗原蛋白分子诱导的CD4+T细胞 关节。这项建议建议使用HLA-DR TRG小鼠来开发一种 靶向控制的多肽免疫调节治疗 这一过程。 与RA易感性相关的HL-DRB*0401和*0405 TRG小鼠， 将用于确定人的免疫原性多肽表位 产生抗原特异性T细胞杂交瘤的自身抗原蛋白 用人类蛋白免疫这些小鼠。两个这样的人体关节 人类II型胶原(HCII)蛋白质，滑膜的主要成分 软骨和人软骨细胞糖蛋白39(HCgp39)可诱导 *0401 TRG小鼠的关节炎。40%的RA患者的T细胞可以 对HCgp39作出回应。人类白细胞抗原-DR4TRG小鼠模型可能是一种重要的 测试类风湿关节炎新型多肽免疫调节治疗的活体模型 病人。这样的多肽可以用来开发一种狭义的抗原特异性 通过诱导无能或Th1/Th2偏斜来耐受，这会好得多 患者对类风湿关节炎的耐受性比我们通常非常有毒的治疗方法要好 听说过。

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.