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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 1型糖尿病是一种T细胞介导的自身免疫性疾病，导致产生胰岛素的胰岛细胞被破坏。第二类MHC分子是易患糖尿病的单一最重要的遗传因素。我们之前的工作已经确定了小鼠糖尿病II类MHC分子I-Ag7和人类对应分子HL A-DQ8的生化和结构特征。我们现在已经在这项工作的基础上设计出了表达I-Ag7的胰岛肿瘤细胞系，并能够激活从实验小鼠的浸润性胰腺中分离出来的促糖尿病T细胞。未来的实验将集中在使用质谱学来识别激活自身反应性T细胞的I-Ag7结合多肽。第二个相关的目标是鉴定胰岛细胞特异性多肽的全部光谱，并将其用作探针来评估可能针对这些配体的T细胞的谱系。