ANTIGEN PROCESSING IN NITCIITA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 1型糖尿病是一种T细胞介导的自身免疫性疾病，其导致产生胰岛素的胰岛细胞的破坏。II类MHC分子是导致糖尿病发病的最重要的遗传因素。我们先前的工作已经确定了小鼠致糖尿病II类MHC分子I-Ag 7及其人类对应物HLA-DQ 8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了表达I-Ag 7的胰岛细胞肿瘤系，并能够激活从实验小鼠浸润胰腺中分离的致糖尿病T细胞。未来的实验集中在使用质谱来鉴定激活自身反应性T细胞的I-Ag 7结合肽。第二个和相关的目的是鉴定胰岛细胞特异性肽的整个谱，并使用这些肽作为探针来评估可能针对这些配体的T细胞库。

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.