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| Article Authors: | Qin Ouyang; Nathan E Standifer; Huilian Qin; Peter Gottlieb; C Bruce Verchere; Gerald T Nepom; Rusung Tan; Constadina Panagiotopoulos |
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| Article Title: | Recognition of HLA class I-restricted beta-cell epitopes in type 1 diabetes. |
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| Reference ID: | 1007450 |
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| Abstract: | Type 1 diabetes results from the autoimmune destruction of insulin-producing pancreatic beta-cells by cytotoxic T-lymphocytes (CTLs). In humans, few beta-cell epitopes have been reported, thereby limiting the study of beta-cell-specific CTLs in type 1 diabetes. To identify additional epitopes, HLA class I peptide affinity algorithms were used to identify a panel of peptides derived from the beta-cell proteins islet amyloid polypeptide (IAPP), islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), insulin, insulinoma-associated antigen 2 (IA-2), and phogrin that were predicted to bind HLA-A*0201. Peripheral blood mononuclear cells from 24 HLA-A*0201 recent-onset type 1 diabetic patients and 11 nondiabetic control subjects were evaluated for gamma-interferon secretion in response to peptide stimulation in enzyme-linked immunospot assays. We identified peptides IAPP9-17, IGRP215-223, IGRP152-160, islet IA-2(172-180), and IA-2(482-490) as novel HLA-A*0201-restricted T-cell epitopes in type 1 diabetic patients. Interestingly, we observed a strong inverse correlation between the binding affinity of beta-cell peptides to HLA-A*0201 and CTL responses against those peptides in recent-onset type 1 diabetic patients. In addition, we found that self-reactive CTLs with specificity for an insulin peptide are frequently present in healthy individuals. These data suggest that many beta-cell epitopes are recognized by CTLs in recent-onset type 1 diabetic patients. These epitopes may be important in the pathogenesis of type 1 diabetes. |
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| Affiliations: | Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia and British Columbia Children's Hospital, 4480 Oak St., Vancouver, British Columbia V6H 3V4, Canada. |
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| Date: | 2006 |
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| Reference Type: | Literature |
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| PubMed ID: | 17065344 |
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| Journal: | Diabetes |
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| Journal Volume: | 55 |
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| Article Pages: | 3068-74 |
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| Journal ISSN: | 0012-1797 |
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| Article Chemical List: | Epitopes;HLA-A Antigens;Histocompatibility Antigens Class I;Peptide Fragments |
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| Article MeSH List: | Amino Acid Sequence; Antibody Affinity; B-Lymphocytes(immunology ); CD8-Positive T-Lymphocytes(immunology ); Diabetes Mellitus, Type 1(immunology ); Epitopes(genetics; immunology ); HLA-A Antigens(genetics; immunology ); Histocompatibility Antigens Class I(genetics; immunology ); Humans; Insulin-Secreting Cells(immunology ); Peptide Fragments(chemistry ); Reference Values |
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| Curation Last Updated: | 2013-01-30 20:01:31 |
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