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.

项目摘要/摘要 伽马/三角洲()T细胞是一种特殊的免疫细胞，被认为是第一道防线 预防重大感染。众所周知，它们在感染期间被早期激活，如结核病、疟疾、 和细菌性脑膜炎。T细胞利用受体(抗原)识别和应答感染性病原体 表面上的受体，或受体，与感染生物(抗原)或其他分子的部分结合 在受感染的细胞上表明它们的存在。除了通过TCR识别入侵生物之外， 其他“共刺激”和“辅助”表面受体共同产生生化信号以激活 牢房。这会导致蛋白质的释放，从而杀死受感染的细胞(例如，穿孔素)，以及可溶性因子 (例如，细胞因子干扰素和IL-17)，以吸引其他类型的免疫细胞，如中性粒细胞和常规 T细胞，到感染和炎症部位。 令人惊讶的是，人们对受体以及相关的附件和共刺激分子是如何 受体，作用于激活细胞。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一个特殊的连接处 被称为免疫突触，但它是如何组织和功能的尚不清楚。看起来T 细胞必须识别感染生物体的成分，当它们与其他“递呈”分子结合时 在细胞表面。然而，这些分子的同一性以及TCR使用的识别策略 他们，仍然默默无闻。这些关于T细胞如何识别和被感染激活的不确定性 在治疗和有针对性的疫苗接种战略中有效利用它们的主要障碍 这些疾病。 我的目标是利用先进的体外和体内实验来了解T细胞功能的分子基础 成像技术，以确定这些细胞中免疫激活的机制，这些机制对它们在 对感染做出反应。这项工作将导致对这些与医学相关的 免疫细胞，并可能有助于设计策略，通过增强来增强我们的免疫防御 T细胞功能。