CYTOTOXIC T LYMPHOCYTE RESPONSE TO INFLUENZA VIRUS

细胞毒性 T 淋巴细胞对流感病毒的反应

• 批准号: 3480840
• 负责人: Thomas J Braciale
• 金额: $ 25.37万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3480840
• 关键词: CD4 molecule; CD8 molecule; MHC class I antigen; MHC class II antigen; antigen presenting cell; cell mediated lymphocytolysis test; cellular immunity; chick embryo; cytotoxic T lymphocyte; disease /disorder model; epitope mapping; hemagglutination test; laboratory mouse; microorganism immunology; model design /development; peptides; protein biosynthesis; proteins; tissue /cell culture; virus antigen; virus protein

A critical early step in the host response to invading microorganisms is the presentation of microbial proteins to the immune system. This proposal is designed to investigate the mechanism of viral antigen processing and presentation to T lymphocytes. It is a continuation of our ongoing efforts to understand in molecular terms viral antigen recognition by MHC class I restricted CD8+ T lymphocytes and MHC class II restricted CD4+ T lymphocytes in the mouse using the type A influenza viruses as a model system. The proposal focuses on two areas: the analysis of the contribution of residues within and outside of an antigenic site in the formation of the antigenic moiety recognized by T lymphocytes in an infected cell and the definition of the intracellular compartment(s) in which newly synthesized viral polypeptides are processed and presented to T lymphocytes. The experimental approach employs cloned populations of cytolytic CD8+ and CD4+ T lymphocytes and synthetic minigenes along with mutant viral polypeptides to probe processing and presentation events in the recognition of the influenza hemagglutinin (HA) and nucleocapsid (NP) proteins. The specific aims of this proposal are: i) to characterize the antigenic moieties in the influenza HA recognized by CD8+ T lymphocytes; ii) to examine the pathway by which newly synthesized influenza virus polypeptides are processed and presented to CD4+ T lymphocytes. This investigation should provide basic information on the immune response to an important human pathogen. In addition, these studies should help to elucidate the molecular mechanisms involved in the formation of antigenic epitopes recognized by T lymphocytes and thereby provide a framework for future vaccine design.

宿主对入侵微生物作出反应的一个关键早期步骤是 微生物蛋白质进入免疫系统的过程。这项建议 旨在研究病毒抗原处理的机制和 呈递给T淋巴细胞。这是我们正在进行的努力的延续 从分子水平了解MHC-I类分子对病毒抗原的识别 限制性CD8+T细胞和MHC-II类限制性CD4+T细胞 以甲型流感病毒为模型的小鼠淋巴细胞 系统。该建议侧重于两个方面：分析 抗原点内外残基在细菌中的作用 鸡传染性支气管炎T淋巴细胞识别抗原部分的形成 感染细胞和细胞内隔室(S)的定义 新合成的病毒多肽被加工并呈现给哪些人 T淋巴细胞。实验方法使用了克隆的种群 细胞溶解CD8+和CD4+T细胞及合成的迷你细胞 突变型病毒多肽探测加工和呈递事件 流感血凝素(HA)和核衣壳蛋白(NP)的识别 蛋白质。这项提议的具体目标是：i)描述 流感病毒HA中CD8+T淋巴细胞识别的抗原性部分； 二)研究新合成的流感病毒的传播途径 多肽被加工并呈递给CD4+T淋巴细胞。这 调查应提供有关免疫反应的基本信息 重要的人类病原体。此外，这些研究应该有助于 阐明抗原性形成的分子机制 T淋巴细胞识别的表位，从而提供了一个框架 未来的疫苗设计。