Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Identification of CD8+ T cell targets in the major T1D autoantigen IA-2beta (#151)

Yannick F Fuchs 1 2 , Anne Karasinsky 2 , Marc Weigelt 2 , Carmen Wilhelm 2 , Gregor Jainta 2 , Anette- G Ziegler 1 , Ezio Bonifacio 2
  1. Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München,, Neuherberg, Germany
  2. DFG Center for Regenerative Therapies, Dresden, Germany
CD8+ T cells are involved in the beta-cell destructive autoimmune response in type 1 diabetes (T1D). Knowledge of MHC class I presented epitopes of beta-cell antigens is required to develop reagents and tests for the specific monitoring and characterization of autoreactive CD8+ T cells in human tissue and peripheral blood samples. We used vaccination with DNA vectors encoding for human IA-2beta in HLA-A*0201 transgenic mice to identify CD8+ T cell targets of this major T1D autoantigen. Analyzing CD8+ T cell responses in vaccinated mice using IFNγ ELISpot assays in combination with peptide libraries of human IA-2beta we successfully mapped three target regions (IA-2beta826-834; IA-2beta833-841; IA-2beta877-887) within the antigens c-terminal intracellular domain. Two of these regions contain epitopes that share sequence homology with epitopes described for the related islet autoantigen IA-2. HLA-A*0201 multimers loaded with the central HLA-A*0201 restricted epitopes of the three regions were generated to allow specific staining of IA-2beta reactive CD8+ T cells and were validated with T1D and healthy control blood samples. Taken together this study for the first time describes MHC class I presented epitopes of IA-2beta that can now serve as basis for the detection of CD8+ T cells reactive to this important T1D autoantigen in human samples.