title: Cytotoxic T cells to an epitope in the islet autoantigen IA-2 are not disease-specific.
abstract: Cytotoxic CD8 T lymphocytes (CTL) are effectors of pancreatic islet beta-cell destruction in type 1 diabetes but, with the exception of a single report, CTL to islet antigen peptides have not been identified. We used autologous blood monocyte-derived dendritic cells to elicit HLA-A2-restricted CTL to a peptide, MVWESGCTV (aa 797-805), that is contiguous with a dominant CD4 T-cell epitope in the islet antigen tyrosine phosphatase IA-2. IA-2 peptide-specific CTL activity measured as 51Cr release from autologous lymphoblasts was detected in 2/6 islet antibody-positive relatives at high risk for type 1 diabetes but also in 2/6 closely HLA-matched controls. All subjects had CTL activity to an HLA-A2-restricted Epstein-Barr virus peptide. CTL to the IA-2 self-peptide were therefore not disease-specific, consistent with other evidence that autoreactive T cells are present in healthy individuals.
authors.affiliation: Autoimmunity and Transplantation Division, Royal Melbourne Hospital, Parkville, 3050, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: M C
authors.initials: MC
authors.lastname: Honeyman
authors.forename: L C
authors.initials: LC
authors.lastname: Harrison
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D003713:Dendritic Cells / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000939:Epitopes; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D015789:HLA-A2 Antigen; C096322:ICA512 autoantibody