PERIPHERAL T-CELL TOLERANCE INDUCED BY SUPERANTIGENS

超抗原诱导的外周 T 细胞耐受

• 批准号: 2066495
• 负责人: David Linn Perkins
• 金额: $ 11.44万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2066495
• 关键词: B lymphocyte; CD4 molecule; CD8 molecule; MHC class I antigen; MHC class II antigen; T cell receptor; T lymphocyte; anergy; antigens; autoimmune disorder; bacterial antigens; biological models; cell cell interaction; cell sorting; disease /disorder model; experimental allergic encephalomyelitis; genetically modified animals; immune tolerance /unresponsiveness; immunization; interleukin 2; interleukin 4; laboratory mouse; lymphocyte proliferation; monoclonal antibody; myelin basic proteins; northern blottings; pathologic process; pertussis toxin; superantigens; thymectomy

The focus of this project is the investigation of immune tolerance in an in vivo model using T cell receptor transgenic mice. Our laboratory has developed an experimental model of T cell tolerance induced by bacterial superantigens in transgenic mice. Because all T cells in the transgenic mice express the Vbeta8.2 transgene, tolerization with the SEB superantigen affects all of the T cells. Following tolerization, we have demonstrated that immune responses are inhibited in an antigen specific manner. WE have transferred the Vbeta8.2 transgene into SJL mice and demonstrated that they respond to the immunodominant T cell epitope of myelin basic protein, mimicked by the synthetic peptide spanning amino acids 89-101 of myelin basic protein, which is the auto-antigen in this disease. Using this model of autoimmune disease, we will investigate the mechanisms of T cell tolerance and clonal anergy in peptide specific autoimmune responses modulated by tolergenic doses of the superantigen SEB. In addition, we will construct alphabeta T cell receptor transgenic mice which specifically recognize a synthetic peptide epitope. These transgenic mice will be used to investigate the mechanism of peptide specific tolerance in vivo.

本项目的重点是研究免疫耐受性在一个 使用T细胞受体转基因小鼠的体内模型。 本实验室 建立了细菌诱导T细胞耐受的实验模型， 转基因小鼠中的超抗原。 因为转基因细胞中的所有T细胞 小鼠表达V β 8.2转基因，用SEB超抗原耐受 影响所有的T细胞。 在耐受化之后，我们已经证明 免疫反应以抗原特异性方式被抑制。 我们有 将V β 8.2转基因转移到SJL小鼠中，并证明它们 对髓鞘碱性蛋白的免疫显性T细胞表位产生应答， 由跨越髓鞘的氨基酸89-101的合成肽模拟 碱性蛋白，这是这种疾病的自身抗原。 利用该模型 自身免疫性疾病，我们将研究T细胞的机制， 肽特异性自身免疫反应中的耐受和克隆无能 由超抗原SEB的耐受性剂量调节。 另外我们 将构建α-T细胞受体转基因小鼠， 识别合成肽表位。 这些转基因小鼠将被用于 探讨体内肽特异性耐受的机制。