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

Benaroya Research Inst At Virginia Mason, Seattle WA

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Abstract

[unreadable] 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. [unreadable] 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. [unreadable] 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. [unreadable] [unreadable] [unreadable]