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.

我小组的主要目标是研究抗原特异性细胞毒性 T 细胞 (CTL) 的功能，重点关注影响 CTL 控制病毒感染和癌症进展的因素。虽然在人类感染期间，强有力且适当的 T 细胞反应通常对宿主有益，但微弱或不适当的反应可能无效，甚至产生有害影响。在过去的二十年里，我们一直致力于了解 T 细胞在多种不同病毒感染和癌症中有效控制病毒所需的关键因素。为此，我们针对从组织和血液中分离的抗原特异性 T 细胞建立了离体和体外 T 细胞功能评估平台。通过将这些功能数据与多组学单细胞和 T 细胞受体 (TCR) 库分析联系起来，我们确定了增强和控制免疫反应的潜在靶点和途径，作为改善包括 SARS-CoV-2 病毒感染在内的几种重要人类疾病结果的一种方法。在本提案中，我们将解决病毒感染和疫苗接种后 CTL 记忆诱导、中枢记忆建立和维持的基本问题，特别关注使用 SARS-CoV-2 作为模型系统的组织驻留记忆细胞。我们的目标是建立 CTL 与有效病毒控制和受影响器官中潜在有害免疫病理学的功能相关性。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。