Identification of a β-Cell-Specific HLA Class I Restricted Epitope in Type 1 Diabetes

Identification of a β-Cell-Specific HLA Class I Restricted Epitope in Type 1 Diabetes Constadina Panagiotopoulos 1 2 , Huilian Qin 1 , Rusung Tan 1 and C. Bruce Verchere 1 1 Department of Pathology & Laboratory Medicine, B.C. Research Institute for Children’s and Women’s Health, Vancouver, British Columbia, Canada 2 Endocrinology and Diabetes Unit, Department of Pediatrics, British Columbia’s Children’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada Address correspondence and reprint requests to Dr. C. Bruce Verchere or Dr. Rusung Tan, Department of Pathology & Laboratory Medicine, BCRICWH, 950 W 28th Ave., Vancouver, British Columbia, Canada, V5Z 4H4. E-mail: verchere{at}interchange.ubc.ca or roo{at}interchange.ubc.ca Abstract Type 1 diabetes is an autoimmune disease in which pancreatic β-cells are destroyed by cytotoxic T-cells that recognize peptide epitopes presented by HLA class I molecules. The identification of human β-cell epitopes may significantly improve the prospects for immunodiagnosis and immunotherapy in type 1 diabetes. Using algorithms to predict nonameric β-cell peptides that would bind to the common HLA allele, HLA-A*0201, we identified a potential epitope from the leader sequence of islet amyloid polypeptide (human islet amyloid polypeptide [IAPP] precursor protein [preproIAPP] 5-13: KLQVFLIVL). Peripheral blood mononuclear cells (PBMCs) were isolated from 18 HLA-A*0201 patients with type 1 diabetes (9 with recent-onset [180 days; range, 183–3,273 days]) and 9 healthy, nondiabetic control subjects. PBMCs were screened for peptide recognition using interferon-γ enzyme-linked immunospot (ELISpot) assays. Of the nine patients with recent-onset type 1 diabetes, six had ELISpot responses to preproIAPP 5-13 that were >3 SDs above the mean of the nondiabetic control subjects ( P = 0.002). In contrast, no patients with type 1 diabetes for >180 days had a response above this threshold. In summary, preproIAPP 5-13 is a novel HLA class I epitope recognized by a significant proportion of cytotoxic T-cells from HLA-A*0201 patients with recent-onset type 1 diabetes and may prove to be a useful tool for the prediction and/or prevention of this disease. ELISpot, enzyme-linked immunospot HCV, hepatitis C virus IAPP, islet amyloid polypeptide MHC, major histocompatibility complex PBMC, peripheral blood mononuclear cell PHA, phytohemagglutinin preproIAPP, IAPP