Epitope Specificity of RSV Nucleoprotein-Specific T Cel*

RSV 核蛋白特异性 T 细胞的表位特异性*

• 批准号: 6754437
• 负责人: James E Crowe
• 金额: $ 4.03万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6754437
• 关键词: Africa; B lymphocyte; MHC class I antigen; cellular immunity; clinical research; cooperative study; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; epitope mapping; gene mutation; human subject; human tissue; humoral immunity; major histocompatibility complex; monoclonal antibody; nucleoproteins; respiratory disorder; respiratory syncytial virus; restriction mapping; tissue /cell culture; virus infection mechanism; virus protein

DESCRIPTION (provided by applicant) Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness in infants and children throughout the world. The immune correlates of protection and resolution of infection are not well defined. Experiments in animal models suggest that RSV induces cytolytic T cells (CTL) that are important to clearance of virus infection. The importance of RSV-specific T cells in the human response to infection is unknown. Currently, reagents and techniques do not exist for the study of RSV-specific T cells in humans. The specific aim of this proposal is to identify the epitope specificity and MHC restriction of RSV nucleoprotein-specific CD8+ CTL in adults. Human peripheral blood mononuclear cells will be used as a source of CD8+ lymphocytes to map the epitope specificity and define the MHC class I allelic restriction of RSV-specific CTL. Defining CTL epitopes will allow improvements in the sensitivity of CTL detection, and provide an opportunity to perform precursor frequency analysis. This project enhances the U.S. Investigator's NIH-supported research by studying the molecular basis for RSV-specific T-cell reactivity, thereby complementing work on RSV-specific B cell responses. The two projects fall within the same area of investigation, namely molecular definition of determinants of human immune responses to RSV, but do not overlap because one studies humoral and the other cellular immunity. Together the grants will allow a coordinated investigation of the major mediators of resistance to infection with RSV.

描述（由申请人提供）呼吸综合病毒（RSV）是全世界婴儿和儿童病毒下呼吸道疾病的最重要原因。保护和感染的分辨率的免疫相关性没有很好地定义。动物模型中的实验表明，RSV诱导细胞溶解T细胞（CTL），这对于清除病毒感染很重要。 RSV特异性T细胞在人类对感染的反应中的重要性尚不清楚。目前，对于人类RSV特异性T细胞的研究，不存在试剂和技术。该建议的具体目的是确定成人RSV核蛋白特异性CD8+ CTL的表位特异性和MHC限制。人外周血单核细胞将用作CD8+淋巴细胞的来源，以绘制表位特异性并定义MHC I类等位基因限制RSV特异性CTL。定义CTL表位将允许改善CTL检测的灵敏度，并提供了进行前体频率分析的机会。该项目通过研究RSV特异性T细胞反应性的分子基础来增强美国研究人员的NIH支持研究，从而补充了RSV特异性B细胞反应的工作。这两个项目属于同一研究领域，即对人类免疫反应的决定因素的分子定义，但由于一个研究体液和其他细胞免疫而不会重叠。补助金将允许对RSV感染的主要耐药性介体进行协调调查。