Autoantibodies and associated T-cell responses to determinants within the 831–860 region of the autoantigen IA-2 in Type 1 diabetes
| Autor: | Michael R. Christie, Patricia A. McKinney, Rossitza Ananieva-Jordanova, J. Lo, Jadwiga Furmaniak, J. M. Tremble, Charlotte Stephenson, H. J. Bodansky, Sarah M. Weenink, B. Rees Smith |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Adolescent medicine.drug_class T-Lymphocytes Immunology Antigen presentation Epitopes T-Lymphocyte Monoclonal antibody medicine.disease_cause Autoantigens Epitope Autoimmunity Interferon-gamma Young Adult medicine Humans Immunology and Allergy Receptor-Like Protein Tyrosine Phosphatases Class 8 Child Autoantibodies biology ELISPOT Autoantibody Antibodies Monoclonal Infant Primary and secondary antibodies Interleukin-10 Diabetes Mellitus Type 1 Amino Acid Substitution biology.protein Female Antibody |
| Zdroj: | Journal of Autoimmunity. 33:147-154 |
| ISSN: | 0896-8411 |
| DOI: | 10.1016/j.jaut.2009.04.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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