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Identification of a β-Cell-Specific HLA Class I Restricted Epitope in Type 1 Diabetes.
- Source :
- Diabetes; Nov2003, Vol. 52 Issue 11, p2647-2651, 5p, 1 Diagram, 3 Charts
- Publication Year :
- 2003
-
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, 1-120 days] and 9 with long-standing diabetes [>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, preprolAPP 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- DIABETES
PANCREATIC beta cells
HLA histocompatibility antigens
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 52
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 11276286
- Full Text :
- https://doi.org/10.2337/diabetes.52.11.2647