HLA-DR4–Associated T and B Cell Responses to Specific Determinants on the IA-2 Autoantigen in Type 1 Diabetes
| العنوان: | HLA-DR4–Associated T and B Cell Responses to Specific Determinants on the IA-2 Autoantigen in Type 1 Diabetes |
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| المؤلفون: | Kerry A. McLaughlin, Diana Morgan, C. C. Richardson, H. Jonathan Bodansky, Kavita Gulati, Richard G. Feltbower, Michael R. Christie |
| المصدر: | The Journal of Immunology. 193:4448-4456 |
| بيانات النشر: | The American Association of Immunologists, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Male, Adolescent, T-Lymphocytes, medicine.medical_treatment, T cell, Immunology, Biology, Autoantigens, Article, Epitope, Immunophenotyping, Epitopes, Young Adult, HLA-DR4 Antigen, medicine, Humans, Immunology and Allergy, Receptor-Like Protein Tyrosine Phosphatases, Class 8, Child, Alleles, B cell, Autoantibodies, B-Lymphocytes, ELISPOT, Autoantibody, FOXP3, Interleukin-10, Interleukin 10, Diabetes Mellitus, Type 1, Phenotype, Cytokine, medicine.anatomical_structure, Female, Peptides |
| الوصف: | Autoantibodies to IA-2 in Type 1 diabetes are associated with HLA-DR4, suggesting influences of HLA-DR4 restricted T-cells on IA-2-specific B-cell responses. The aim of this study was to investigate possible T-B-cell collaboration by determining whether autoantibodies to IA-2 epitopes are associated with T-cell responses to IA-2 peptides presented by DR4. T-cells secreting the cytokines interferon-γ and interleukin-10 in response to seven peptides known to elicit T-cell responses in Type 1 diabetes were quantified by cytokine ELISPOT in HLA-typed patients characterised for antibodies to IA-2 epitopes. T-cell responses were detected to all peptides tested, but only interleukin-10 responses to 841-860 and 853-872 peptides were associated with DR4. Phenotyping by RT-PCR of FACS-sorted CD45ROhi T-cells secreting interleukin-10 in response to these two peptides indicated that these expressed GATA-3 or T-bet, but not FoxP3, consistent with these being Th2 or Th1 memory T-cells rather than of regulatory phenotype. T-cell responses to the same two peptides were also associated with specific antibodies; those to 841-860 peptide with antibodies to juxtamembrane epitopes, which appear early in pre-diabetes, and those to peptide 853-872 with antibodies to an epitope located in the 831-862 central region of the IA-2 tyrosine phosphatase domain. Antibodies to juxtamembrane and central region constructs were both DR4-associated. This study identifies a region of focus for B- and T-cell responses to IA-2 in HLA-DR4 diabetic patients that may explain HLA- associations of IA-2 autoantibodies and this region may provide a target for future immune intervention to prevent disease. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09daf71f63fedb6cc10055bad7df6f8eTest https://doi.org/10.4049/jimmunol.1301902Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....09daf71f63fedb6cc10055bad7df6f8e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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