ANTIGEN PROCESSING IN NITCIITA

NITCIITA 中的抗原处理

• 批准号: 8168713
• 负责人: EMIL Raphael UNANUE
• 金额: $ 0.62万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-10 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168713
• 关键词: Autoimmune Diseases; Binding; Biochemical; Cells; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Engineering; Funding; Future; Grant; HLA-DQ8 antigen; Histocompatibility Antigens Class II; Human; Institution; Insulin; Insulin-Dependent Diabetes Mellitus; Islets of Langerhans; Ligands; Mass Spectrum Analysis; Mediating; Mus; Pancreas; Peptides; Research; Research Personnel; Resources; Source; T-Lymphocyte; Tumor Cell Line; United States National Institutes of Health; Work; antigen processing; autoreactive T cell; genetic element; islet; research study; single molecule

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 1 diabetes mellitus is a T cell-mediated autoimmune disorder that results in the destruction of insulin-producing pancreatic islet ¿ cells. The class II MHC molecules are the single-most important genetic element that predispose to onset of diabetes. Our previous work has defined the biochemical and structural features of the murine diabetogenic class II MHC molecule, I-Ag7, and its human counterpart, HLA-DQ8. We have now built upon this work to engineer islet ¿ cell tumor lines that express I-Ag7 and are able to activate diabetogenic T cells isolated from infiltrated pancreas of experimental mice. The future experiments are focused on using mass spectrometry to identify I-Ag7-bound peptides that activate autoreactive T cells. A second and related aim is to identify the entire spectrum of islet ¿ cell-specific peptides and use these as probes to evaluate the repertoire of T cells that maybe directed against these ligands.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 1 型糖尿病是一种 T 细胞介导的自身免疫性疾病，会导致产生胰岛素的胰岛细胞遭到破坏。 II 类 MHC 分子是导致糖尿病发病的最重要的遗传因素。我们之前的工作已经确定了小鼠糖尿病 II 类 MHC 分子 I-Ag7 及其人类对应物 HLA-DQ8 的生化和结构特征。现在，我们以这项工作为基础，设计了表达 I-Ag7 的胰岛细胞肿瘤系，并能够激活从实验小鼠浸润性胰腺中分离出的致糖尿病 T 细胞。未来的实验重点是使用质谱法来鉴定可激活自身反应性 T 细胞的 I-Ag7 结合肽。第二个相关目标是鉴定胰岛细胞特异性肽的整个谱系，并使用它们作为探针来评估可能针对这些配体的 T 细胞库。