MICROBIAL SUPERANTIGENS AND AUTOIMMUNITY

微生物超抗原和自身免疫

• 批准号: 3147781
• 负责人: STEVEN M FRIEDMAN
• 金额: $ 20.17万
• 依托单位: HOSPITAL FOR SPECIAL SURGERY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-15 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3147781
• 关键词: B lymphocyte; T cell receptor; T lymphocyte; antibody formation; athymic mouse; autoimmune disorder; bacterial toxins; biological signal transduction; cell cell interaction; human tissue; immunofluorescence technique; immunoglobulin G; immunoglobulin M; laboratory mouse; leukocyte activation /transformation; monoclonal antibody; myelin basic proteins; tissue /cell culture

Studies of pathogenic T cells in both animal models of autoimmune disease and spontaneously arising autoimmune disorders in man have demonstrated the selective use of particular T cell receptor (TCR) beta chain variable (V) genes. The recent characterization of a class of microbial products, termed superantigens (SA), which are mitogenic for T cells based on TCR Vbeta gene usage, suggests that microbial SA may provide the link between infection and autoimmunity. While clinically recognized syndromes attributable to SA are often characterized by shock and immunosuppression, our laboratory has recently demonstrated the immunostimulatory effects of some microbial SA on the humoral arm of the human immune system. The objective of this proposal is to analyze three proposed mechanisms by which microbial SA may function to stimulate the immune system and, by extension, may lead to autoimmunity. Specifically, we propose to investigate: 1) the mechanisms by which microbial SA promote T cell-dependent B cell activation; 2) the activation signal delivered to B cells by direct SA binding; 3) the potential for microbial SA to activate normally quiescent autoreactive T cells; 4) the role of microbial SA and microbial SA-reactive T cells in animal models of autoimmunity.

两种自身免疫性疾病动物模型中致病性T细胞的研究 和自发性自身免疫性疾病已经证明了 选择性使用特定T细胞受体（TCR）β链可变区（V） 基因. 最近对一类微生物产物的表征， 称为超抗原（SA），其基于TCR对T细胞是促有丝分裂的 Vbeta基因的使用，表明微生物SA可能提供了之间的联系， 感染和自身免疫。 虽然临床上公认的综合征 可归因于SA的疾病通常以休克和免疫抑制为特征， 我们的实验室最近证明了 一些微生物SA在人类免疫系统的体液臂上。 的 本提案的目的是分析三种拟议机制，通过这些机制 微生物SA可以起到刺激免疫系统的作用，并且，通过扩展， 可能导致自身免疫 具体而言，我们建议调查：1） 微生物SA促进T细胞依赖性B细胞 激活; 2）通过直接SA传递到B细胞的激活信号 结合; 3）微生物SA激活正常静止的潜力 自身反应性T细胞; 4）微生物SA和微生物SA反应性T细胞的作用 自身免疫动物模型中的T细胞。