Epitopes described in "Recognition of HLA class I-restricted beta-cell epitopes in type 1 diabetes."

Article Authors:Qin Ouyang; Nathan E Standifer; Huilian Qin; Peter Gottlieb; C Bruce Verchere; Gerald T Nepom; Rusung Tan; Constadina Panagiotopoulos
Article Title:Recognition of HLA class I-restricted beta-cell epitopes in type 1 diabetes.
Reference Detail
Reference ID:1007450
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.
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.
Reference Type:Literature
PubMed ID:17065344
Journal Volume:55
Article Pages:3068-74
Journal ISSN:0012-1797
Article Chemical List:Epitopes;HLA-A Antigens;Histocompatibility Antigens Class I;Peptide Fragments
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
Curation Last Updated:2014-10-03 20:56:45