PERIPHERAL T CELL TOLERANCE INDUCED BY SUPERANTIGENS

超抗原诱导的外周 T 细胞耐受

• 批准号: 3455879
• 负责人: David Linn Perkins
• 金额: $ 18.2万
• 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 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3455879
• 关键词: B lymphocyte; CD4 molecule; CD8 molecule; MHC class I antigen; MHC class II antigen; T cell receptor; T lymphocyte; 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; 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儿童免疫耐受情况。 体内模型采用T细胞受体转基因小鼠。我们的实验室有 细菌诱导T细胞耐受实验模型的建立 转基因小鼠体内的超抗原。因为转基因中的所有T细胞 小鼠表达Vbeta8.2转基因，对SEB超抗原耐受 影响所有的T细胞。在容忍之后，我们已经展示了 免疫反应以一种抗原特异性的方式被抑制。我们有 将Vbeta8.2转基因导入SJL小鼠，并证明它们 对髓鞘碱性蛋白的免疫优势T细胞表位做出反应， 由髓鞘89-101氨基酸组成的合成肽模拟 碱性蛋白，这是这种疾病中的自身抗原。使用此模型 对于自身免疫性疾病，我们将研究T细胞的机制 多肽特异性自身免疫反应中的耐受性和克隆性无能 受超抗原SEB耐受量的调节。此外，我们 将构建具有特异性的Alphabeta T细胞受体转基因小鼠 识别人工合成的多肽表位。这些转基因小鼠将被用于 探讨体内多肽特异性耐受的机制。