T-cell lines reactive to an immunodominant epitope of the tyrosine phosphatase-like autoantigen IA-2 in type 1 diabetes

Hawkes, C. J. and Schloot, N. C. and Marks, J. and Willemen, S. J. M. and Drijfhout, J. W. and Mayer, E. K. and Christie, M. R. and Roep, B. O. (2000) T-cell lines reactive to an immunodominant epitope of the tyrosine phosphatase-like autoantigen IA-2 in type 1 diabetes. Diabetes, 49 (3). pp. 356-366. ISSN 0012-1797

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Abstract

Type 1 diabetes is the result of destruction of the insulin-secreting β-cells of the pancreas by a process in which T-cells play a central role. A tyrosine phosphatase-like protein, IA-2, is a major target for autoantibodies and T-cells in the disease. In this study, we have further characterized the T-cell response to IA-2 by the generation and characterization of T-cell lines. T-cell lines responsive to IA-2 antigen were generated from 17 of 32 patients and 3 of 10 control subjects. Antigen specificity was confirmed in lines from six diabetic patients and one control individual by demonstration of responses to synthetic IA-2 peptides and epitope mapping. Five lines from diabetic patients responded to one of two peptides representing amino acids 831-850 and 841-860 of IA-2. The overlapping portion may therefore represent an immunodominant region of the molecule. The sixth patient-derived line responded to a peptide representing amino acids 751-770 of IA-2 presented by the DR 4 (DRBl*0401) allele that confers susceptibility to type 1 diabetes. Primary T-cell responses to peptides of the immunodominant region were detected in 9 of 19 (47) type 1 diabetic patients and 16 of 22 (73) nondiabetic siblings, consistent with this region having immunostimulatory properties. The study reports for the first time T-cell lines reactive to IA-2 from diabetic patients and defines an immunodominant region of the molecule.

Keywords:autoantigen, adolescent, antigen specificity, article, child, clinical article, controlled study, disease predisposition, gene mapping, genetic susceptibility, human, immunostimulation, insulin dependent diabetes mellitus, pancreas islet beta cell, priority journal, T lymphocyte, Adolescent, Autoantigens, Cell Line, Child, Preschool, Cytoplasm, Diabetes Mellitus, Type 1, Epitopes, Female, HLA Antigens, Humans, Immunodominant Epitopes, Infant, Male, Membrane Glycoproteins, Membrane Proteins, Peptide Fragments, Protein-Tyrosine-Phosphatase, T-Lymphocytes
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:18140
Deposited On:31 Jul 2015 09:41

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