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Recognition of HLA Class I–Restricted β-Cell Epitopes in Type 1 Diabetes
- Source :
- Diabetes. 55:3068-3074
- Publication Year :
- 2006
- Publisher :
- American Diabetes Association, 2006.
-
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.
- Subjects :
- Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Antibody Affinity
Human leukocyte antigen
CD8-Positive T-Lymphocytes
Biology
Epitope
Epitopes
Antigen
Reference Values
Insulin-Secreting Cells
Internal Medicine
medicine
Humans
Cytotoxic T cell
Amino Acid Sequence
Peptide sequence
B-Lymphocytes
Type 1 diabetes
HLA-A Antigens
Insulin
Histocompatibility Antigens Class I
medicine.disease
Peptide Fragments
CTL
Diabetes Mellitus, Type 1
Immunology
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 55
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....e7a570963e8b627a61268b06e4b4ec73