التفاصيل البيبلوغرافية
| العنوان: |
Recognition of HLA Class I-Restricted β-Cell Epitopes in Type 1 Diabetes. |
| المؤلفون: |
Qin Ouyang1, Standifer, Nathan E.2, Huilian Qin1, Gottlieb, Peter3, Verchere, C. Bruce1, Nepom, Gerald T.2, Rusung Tan1 roo@interchange.ubc.ca, Panagiotopoulos, Constadina4 |
| المصدر: |
Diabetes. Nov2006, Vol. 55 Issue 11, p3068-3074. 7p. 1 Chart, 4 Graphs. |
| مصطلحات موضوعية: |
*DIABETES, *LIVER cells, *PROTEINS, *PEPTIDES, *PEOPLE with diabetes |
| مستخلص: |
Type 1 diabetes results from the autoimmune destruction of insulin-producing pancreatic β-cells by cytotoxic T-lymphocytes (CTLs). In humans, few β-cell epitopes have been reported, thereby limiting the study of β-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 β-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 γ-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 β-cell peptides to HLA-A*0201 and CTL responses against those peptides in recent-onset type I 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 β-cell epitopes are recognized by CTLs in recent-onset type I diabetic patients. These epitopes may be important in the pathogenesis of type 1 diabetes. Diabetes 55:3068-3074, 2006 [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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