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.

项目总结/摘要 γ/δ（γ/δ）T细胞是专门的免疫细胞，被认为是第一道防线 主要感染。已知它们在结核病、疟疾等感染的早期被激活， 和细菌性脑膜炎巨噬细胞T细胞使用受体（巨噬细胞抗原）识别并应答感染因子 受体，或TCR），其与感染生物体（抗原）或其他分子的部分结合 感染的细胞上显示它们的存在除了通过免疫球蛋白TCR识别入侵生物外， 其它“共刺激”和“辅助”表面受体协同产生生物化学信号， 牢房这导致蛋白质的释放，杀死感染的细胞（如。穿孔素），以及可溶性因子 （例如：细胞因子IFN γ和IL-17），其吸引其他类型的免疫细胞，如嗜中性粒细胞和常规免疫细胞。 免疫抑制性T细胞，感染和炎症部位。 令人惊讶的是，关于树突状细胞TCR，沿着与相关的辅助和共刺激因子如何在细胞内表达， 受体，工作来激活细胞。这些分子间的相互作用共同构成了抗原 识别，被认为发生在一个专门的交界处，形成之间的淋巴细胞和感染的细胞 免疫突触，但它是如何组织和功能尚不清楚。似乎也是如此 当感染有机体的成分与其他“呈递”分子结合时，细胞必须识别它们 在细胞表面。然而，这些分子的身份和TCR识别的策略， 他们，依然默默无闻。这些不确定性是关于CD 34 + T细胞如何识别并被感染激活 在治疗和针对性的疫苗接种战略中， 这些疾病。 我的目的是利用先进的体外和体内研究方法， 成像技术，以确定这些细胞中的免疫激活机制，这些机制对它们在以下方面的作用至关重要： 应对感染。这项工作将导致更详细地了解这些医学相关的 免疫细胞，并可能有助于设计的战略，以加强我们的免疫防御，通过提高免疫细胞， T细胞功能