Functional HLA-A*201-peptide and DR0401-peptide microarrays for Type 1 diabetes

描述（由申请人提供）：I型糖尿病（T1D）是一种T细胞介导的自身免疫性疾病。了解疾病特异性T细胞在T1D中的作用一直是免疫学家在T1D研究中的关键追求。CD4+和CD8+ T细胞都参与了T1D的发病机制。然而，缺乏一种可以同时监测CD4+和CD8+糖尿病T细胞的T细胞检测方法。

DESCRIPTION (provided by applicant): Type I diabetes (T1D) is a T cell mediated autoimmune disease. The understanding of disease specific T cells in T1D has been the key pursuit for immunologists in T1D research. Both CD4+ and CD8+ T cells are involved in T1D pathogenesis. However, a T cell assay that can monitor both CD4+ and CD8+ diabetogenic T cells is lacking. In this current application, we propose to develop functional microarray chips to assay for the presence of islet antigen specific CD4+ and CD8+ T cells in the peripheral blood of diabetic subjects. The use of microarray chips will allow the monitoring of T cells specific for multiple islet antigens with a fairly low volume of blood. In addition, cytokine and chemokine capturing antibodies will be immobilized together with the MHC/peptide, allowing detection of the cytokines and chemokines secreted by the islet specific T cells. The specific objectives includes 1) Developing proteomic chips to detect HLA-A2*0201 and DRA/DRB1*0401 restricted islet antigen specific T cells, and to measure the cytokine and chemokine profiles of these autoreactive T cells. 2) Developing experimental protocols for monitoring islet antigen specific CD4+ and CD8+ T cells and evaluating of the reproducibility of the assay and 3) Tracking islet antigen specific T cells in diabetic subjects in a longitudinal study.