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. ? ? ?
| Ge, Xinhui; James, Eddie A; Reijonen, Helena et al. (2011) Differences in self-peptide binding between T1D-related susceptible and protective DR4 subtypes. J Autoimmun 36:155-60 |
| Ge, Xinhui; Gebe, John A; Bollyky, Paul L et al. (2010) Peptide-MHC cellular microarray with innovative data analysis system for simultaneously detecting multiple CD4 T-cell responses. PLoS One 5:e11355 |
