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

Hawkes, C. J., Schloot, N. C., Marks, J., Willemen, S. J. M., Drijfhout, J. W., Mayer, E. K., 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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