STRUCTURAL STUDIES OF GLYCOLIPID-REACTIVE T CELLS AND ANTIBODIES

糖脂反应性 T 细胞和抗体的结构研究

• 批准号: 8362144
• 负责人: Dirk M Zajonc
• 金额: $ 0.41万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362144
• 关键词: Adjuvant; Agonist; Animal Model; Antibodies; Antigen Presentation; Antigens; B-Lymphocytes; Borrelia burgdorferi; Cells; Complex; Development; Epitopes; Family; Funding; Glycolipids; Grant; Immune; Immune system; Institutes; Lipid Binding; Lipids; Lyme Disease; Multiple Sclerosis; Mus; National Center for Research Resources; Patients; Principal Investigator; Radiation; Research; Research Infrastructure; Resources; Source; T-Lymphocyte; United States National Institutes of Health; Work; base; chemotherapeutic agent; cost; immune function; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The CD1 family of antigen presenting molecules presents a wide variety of glycolipid antigens to lipid-specific T cells, resulting in their activation and expansion, necessary to carry out various immune functions including the activation of other immune cells. Structural studies of various CD1-lipid-TCR complexes will greatly enhance our understanding of glycolipid antigen presentation and recognition in the immune system. The gained structural results can potentially be used for the development of lipid based chemotherapeutic agents or adjuvants to target various immune conditions, such as Multiple Sclerosis (MS) or lyme disease. The immunomodulatory functions of these compounds can be assessed using animal models in our institute. In that regard we are working on one hand with T cells that are enriched in MS patients and on the other hand we have already crystallized mouse CD1d with a potential T cell agonist from Borrelia burgdorferi, the causative agent of Lyme disease. Furthermore we have obtained antibodies, which can discriminate between different CD1d-bound lipids. A ternary complex between CD1d-lipid-Fab will provide a detailed comparison of the recognition and interaction with specific glycolipid epitopes between T cells and B cells.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 CD1 抗原呈递分子家族向脂质特异性 T 细胞呈递多种糖脂抗原，导致其激活和扩增，这是执行各种免疫功能（包括激活其他免疫细胞）所必需的。各种 CD1-脂质-TCR 复合物的结构研究将极大地增强我们对免疫系统中糖脂抗原呈递和识别的理解。所获得的结构结果可用于开发基于脂质的化疗剂或佐剂，以针对多种免疫疾病，例如多发性硬化症（MS）或莱姆病。这些化合物的免疫调节功能可以使用我们研究所的动物模型进行评估。在这方面，我们一方面正在研究多发性硬化症患者体内富集的 T 细胞，另一方面，我们已经用来自伯氏疏螺旋体（莱姆病的病原体）的潜在 T 细胞激动剂结晶了小鼠 CD1d。此外，我们还获得了可以区分不同 CD1d 结合脂质的抗体。 CD1d-lipid-Fab 之间的三元复合物将提供 T 细胞和 B 细胞之间与特定糖脂表位的识别和相互作用的详细比较。