Human antigen-specific T cell responses in viral control and immunopathology

病毒控制和免疫病理学中的人类抗原特异性 T 细胞反应

• 批准号: MR/Y015347/1
• 负责人: Tao Dong
• 金额: $ 180.04万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY015347%2F1
• 关键词: Human; antigen; specific; cell; responses

The main objective of my group is to investigate the functional aspects of antigen specific cytotoxic T cells (CTL) with a focus on the factors affecting CTL in controlling virus infection and cancer progression.While a robust and appropriate T cell response is typically beneficial to the host during human infections, a weak or inappropriate response can be ineffective or even have a detrimental effect. Over the past two decades, our efforts have been on understanding the key factors required for efficient viral control by T cells in a number of different viral infections and cancer. To do this, we have established an ex-vivo and in-vitro T cell functional evaluation platforms for antigen-specific T cells isolated from tissue and blood. By linking these functional data with multi-omic single cell and T cell receptor (TCR) repertoire analysis, we have identified potential targets and pathways to augment and control the immune response as a way of improving the outcome of several important human diseases including SARS-CoV-2 virus infection. In this proposal, we will address fundamental questions in CTL memory induction, central memory establishment and maintenance following virus infection and vaccination, with a particular focus on tissue-resident memory cells using SARS-CoV-2 as the model system. We aim to establish CTL functional relevance to efficient viral control and potential detrimental immunopathology in affected organs. By studying the immunology of tissues, we will provide scientific evidence and tools for improved vaccine design and therapeutic approaches for virus infections.

我小组的主要目的是研究抗原特异性细胞毒性T细胞（CTL）的功能方面，重点是影响CTL控制病毒感染和癌症进展的因素。尽管人类感染期间，稳健且适当的T细胞反应通常对宿主有益，而在人类感染过程中，较弱或不适当的反应可能是不适当的，甚至是无效的效果。在过去的二十年中，我们一直在理解许多不同病毒感染和癌症中T细胞有效控制病毒所需的关键因素。为此，我们为从组织和血液中分离出的抗原特异性T细胞建立了一个前体和体外T细胞功能评估平台。通过将这些功能数据与多矩单细胞和T细胞受体（TCR）曲目分析联系起来，我们已经确定了增强和控制免疫反应的潜在靶标和途径，以改善包括SARS-COV-2病毒感染在内的几种重要人类疾病的结果。在此提案中，我们将在病毒感染和疫苗接种后解决CTL记忆诱导，中央记忆的建立和维护中的基本问题，并特别关注使用SARS-COV-2作为模型系统的组织居住记忆细胞。我们旨在与受影响器官的有效病毒控制和潜在的有害免疫病理学建立CTL功能相关。通过研究组织的免疫学，我们将为改进病毒感染的疫苗设计和治疗方法提供科学证据和工具。