Autoantibodies and associated T-cell responses to determinants within the 831-860 region of the autoantigen IA-2 in Type 1 diabetes

Weenink, S. M. and Lo, J. and Stephenson, C. R. and McKinney, P. A. and Ananieva-Jordanova, R. and Rees Smith, B. and Furmaniak, J. and Tremble, J. M. and Bodansky, H. J. and Christie, Michael R. (2009) Autoantibodies and associated T-cell responses to determinants within the 831-860 region of the autoantigen IA-2 in Type 1 diabetes. Journal of Autoimmunity, 33 (2). pp. 147-154. ISSN 0896-8411

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Autoantibodies and associated T-cell responses to determinants within the 831-860 region of the autoantigen IA-2 in Type 1 diabetes

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Abstract

B-cells influence T-cell reactivity by facilitating antigen presentation, but the role of autoantibody-secreting B-cells in regulating T-cell responses in Type 1 diabetes is poorly defined. The aims of this study were to characterise epitopes on the IA-2 autoantigen for three monoclonal antibodies from diabetic patients by amino acid substitutions of selected residues of IA-2, establish contributions of these epitopes to binding of serum antibodies in Type 1 diabetes and relate B- and T-cell responses to overlapping determinants on IA-2. The monoclonal antibodies recognised overlapping epitopes, with residues within the 831-860 region of IA-2 contributing to binding; substitution of Glu836 inhibited binding of all three antibodies. Monoclonal antibody Fab fragments and substitution of residues within the 831-836 region blocked serum antibody binding to an IA-2 643-937 construct. IL-10-secreting T-cells responding to peptides within the 831-860 region were detected by cytokine-specific ELISPOT in diabetic patients and responses to 841-860 peptide were associated with antibodies to the region of IA-2 recognised by the monoclonal antibodies. The study identifies a region of IA-2 frequently recognised by antibodies in Type 1 diabetes and demonstrates that these responses are associated with T-cells secreting IL-10 in response to a neighbouring determinant. © 2009 Elsevier Ltd. All rights reserved.

Keywords:autoantigen, interleukin 10, islet antigen 2, monoclonal antibody, unclassified drug, adolescent, adult, amino acid substitution, antibody blood level, antibody response, antigen binding, article, B lymphocyte, cellular immunity, child, clinical article, cytokine release, female, human, infant, insulin dependent diabetes mellitus, male, priority journal, T lymphocyte, Adolescent, Antibodies, Monoclonal, Autoantibodies, Autoantigens, Diabetes Mellitus, Type 1, Epitopes, T-Lymphocyte, Humans, Interferon-gamma, Interleukin-10, Receptor-Like Protein Tyrosine Phosphatases, Class 8, T-Lymphocytes, Young Adult
Subjects:C Biological Sciences > C550 Immunology
Divisions:College of Science > School of Life Sciences
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ID Code:18114
Deposited On:05 Aug 2015 13:49

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