Article ViewAbstractThe Review of Diabetic Studies,2009,6,1,43-53.DOI:10.1900/RDS.2009.6.43Published:May 2009Type:Original ArticleAuthors:Sarah Rasche, Rhea Y Busick, and Anthony Quinn Author(s) affiliations:Sarah Rasche, Rhea Y. Busick and Anthony Quinn Department of Biological Sciences, University of Toledo, 2801 W. Bancroft, Toledo, OH 43606, USA. Abstract:Autoimmunity to islet cell antigens like glutamic acid decarboxylase 65kD (GAD65) is associated with the destruction of insulin-producing β-cells and progression to type 1 diabetes (T1D) in NOD mice and humans. T cell responses to GAD65 are detectable in the spleen of prediabetic NOD mice and in the peripheral blood of humans prior to the onset of overt hyperglycemia. Previous findings from our lab revealed that GAD65546-554-specific cytotoxic T lymphocytes (CTL) are present in naïve NOD mice and are able to induce islet inflammation upon adoptive transfer into NOD.scid recipients. Additionally, we found that professional antigen-presenting cells (APC) generate the p546-554 epitope from a soluble GAD65 fragment, p530-554, and from GAD65 released by injured β-cells in vivo. Here, we report that the GAD65 fragment p546-554 is a dominant CTL-inducing epitope which is naturally processed and presented by a GAD65-expressing β-cell line. Further, coculture of GAD65546-554-specific CTL with the β-cells leads to a reduction in insulin production and the induction of perforin-mediated cell death. Collectively, these findings support a role for the cross-presentation of GAD65 antigen in the priming and enhancement of dominant GAD65- specific CTL responses, which can directly target β-cells that display GAD65 epitopes. Keywords:Antigen, Beta-cell, FasL, GAD65, Major histocompatibility complex class I, MHC, NOD.scid, Pathogenesis, T cell, Type 1 diabetesView:PDF (1.01 MB) PDFClick here to download the PDF file. Images Adoptive transfer of GAD65546-554-specific CTL leads to a loss of insulin production in vivo ‹ Inflammation in Diabetic Encephalopathy is Prevented by C-Peptide up Factors Associated with the Prevalence of Diabetes Mellitus Among Elderly Men and Women Living in Mediterranean Islands: The MEDIS Study ›