ANTIGEN PROCESSING IN NITCIITA

NITCIITA 中的抗原处理

• 批准号: 8361361
• 负责人: EMIL Raphael UNANUE
• 金额: $ 2.16万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361361
• 关键词: Autoimmune Diseases; Binding; Biochemical; Cells; Diabetes Mellitus; Engineering; Funding; Future; Grant; HLA-DQ8 antigen; Histocompatibility Antigens Class II; Human; Insulin; Insulin-Dependent Diabetes Mellitus; Islets of Langerhans; Ligands; Mass Spectrum Analysis; Mediating; Mus; National Center for Research Resources; Pancreas; Peptides; Principal Investigator; Research; Research Infrastructure; Resources; Source; T-Lymphocyte; Tumor Cell Line; United States National Institutes of Health; Work; antigen processing; autoreactive T cell; biomedical resource; cost; genetic element; islet; research study

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. 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 1型糖尿病是一种T细胞介导的自身免疫性疾病，可破坏产生胰岛素的胰岛胰岛细胞。 II类MHC分子是易感糖尿病发作的最重要的重要遗传元素。我们以前的工作定义了鼠糖尿病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，我们已经建立在这项工作的基础上，以设计表达I-AG7的细胞肿瘤系，并能够激活从实验小鼠浸润的胰腺中分离出的糖尿病性T细胞。未来的实验集中于使用质谱法识别激活自动反应性T细胞的I-AG7结合的胡椒体。第二个相关的目的是确定整个胰岛特异性辣椒的整个光谱，并将其用作评估可能针对这些配体的T细胞的曲目。