CELLULAR AND MOLECULAR BASIS OF GAMMA/DELTA T CELL ANTIGEN RECOGNITION

Gamma/Delta T 细胞抗原识别的细胞和分子基础

• 批准号: 9101988
• 负责人: Kaushik Choudhuri
• 金额: $ 23.37万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9101988
• 关键词: Address; Animal Model; Antigen Receptors; Antigens; Bacterial Infections; Bacterial Meningitis; Binding; Biochemical; Biological; CD8B1 gene; Cell physiology; Cell surface; Cells; Characteristics; Disease; Epithelial; Event; Genetic; Goals; Histocompatibility Antigens; Human; Imaging technology; Immune; Immunity; Immunologic Monitoring; In Vitro; Infection; Infectious Agent; Inflammation; Inflammatory; Interferons; Interleukin-17; Invaded; Knowledge; Lead; Ligation; Lipids; Lymphocyte; Malaria; Malignant Neoplasms; Mediating; Modality; Molecular; Monitor; Mycobacterium Infections; Neutrophil Infiltration; Organism; Outcome; Parasitic infection; Pathway interactions; Peptides; Property; Proteins; Receptor Signaling; Recruitment Activity; Role; Signal Transduction; Signaling Molecule; Site; Stress; Structure; Surface; T-Lymphocyte; Testing; Therapeutic; Transgenic Mice; Tuberculosis; Uncertainty; Virus Diseases; Work; abstracting; adaptive immunity; base; cytokine; design; experience; functional outcomes; imaging modality; immune activation; immunological synapse; immunological synapse formation; in vivo imaging; killings; mucosal site; neoplastic; neutrophil; pathogen; perforin; preference; receptor; response; spatiotemporal; submicron; targeted treatment; vaccination strategy

PROJECT SUMMARY/ABSTRACT Gamma/delta () T cells are specialized immune cells that are thought to be a first line of defense against major infections. They are known to be activated early during infections such as tuberculosis, malaria, and bacterial meningitis.  T cells recognize and respond to infectious agents using a receptor (the  antigen receptor, or  TCR) on their surface, which binds to parts of infecting organisms (antigens) or other molecules on infected cells that indicate their presence. In addition to recognition of invading organisms by the  TCR, other `costimulatory' and `accessory' surface receptors cooperate to generate biochemical signals to activate the cell. This results in the release of proteins that kill infected cells (eg. perforin), as well as soluble factors (eg. cytokines IFN and IL-17) that attract other types of immune cells, such as neutrophils and conventional  T cells, to sites of infection and inflammation. Surprisingly little is known about how the  TCR, along with associated accessory and costimulatory receptors, work to activate the cell. These molecular interactions, which together form the basis for antigen recognition, is thought to take place at a specialized junction that forms between  T cells and infected cells known as the immunological synapse, but how it is organized and functions is unclear. It also seems that  T cells must recognize components of infecting organisms when they are bound to other `presenting' molecules on the cell surface. However, the identity of these molecules and the strategies used by  TCRs to recognize them, remain obscure. These uncertainties about how  T cells recognize and are activated by infections present major impediments to their effective harnessing in treatments and vaccination strategies targeting these diseases. I aim to understand the molecular underpinnings of  T cell function using advanced in vitro and in vivo imaging technologies, to identify mechanisms of immune activation in these cells that are critical for their role in responding to infections. This work will lead to a more detailed understanding of these medically relevant immune cells, and may contribute to the design of strategies to enhance our immune defenses by boosting  T cell function.

项目概要/摘要 γ/δ () T 细胞是特殊的免疫细胞，被认为是第一道防线 已知它们在结核病、疟疾、 和细菌性脑膜炎  T 细胞使用受体（ 抗原）识别感染因子并做出反应。 受体，或  TCR）位于其表面，与感染生物体的部分（抗原）或其他分子结合 除了通过  TCR 识别入侵生物体之外， 其他“共刺激”和“辅助”表面受体合作产生生化信号以激活 这导致细胞释放杀死受感染细胞的蛋白质（例如穿孔素）以及可溶性因子。 （例如细胞因子 IFN 和 IL-17）吸引其他类型的免疫细胞，例如中性粒细胞和常规细胞  T 细胞，到达感染和炎症部位。 令人惊讶的是，人们对  TCR 以及相关的辅助和共刺激如何发挥作用知之甚少。 这些分子相互作用共同构成了抗原的基础。 识别被认为发生在  T 细胞和感染细胞之间形成的特殊连接处 被称为免疫突触，但它的组织和功能似乎还不清楚。 当细胞与其他“呈递”分子结合时，细胞必须识别感染生物体的成分 然而，这些分子的身份以及  TCR 识别的策略。 关于  T 细胞如何识别感染并被感染激活的这些不确定性仍然不清楚。 对有效利用它们进行治疗和疫苗接种策略构成了主要障碍 这些疾病。 我的目标是利用先进的体外和体内技术来了解  T 细胞功能的分子基础 成像技术，以确定这些细胞中的免疫激活机制，这对于它们的作用至关重要 这项工作将有助于人们更详细地了解这些与医学相关的问题。 免疫细胞，并可能有助于设计通过增强  来增强我们的免疫防御的策略 T细胞功能。