NDLI: HLA-DR4-associated T and B cell responses to specific determinants on the IA-2 autoantigen in type 1 diabetes.

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HLA-DR4-associated T and B cell responses to specific determinants on the IA-2 autoantigen in type 1 diabetes.

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HLA-DR4-associated T and B cell responses to specific determinants on the IA-2 autoantigen in type 1 diabetes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Richardson, Carolyn C. Bodansky, H. Jonathan Feltbower, Richard G. Morgan, Diana Gulati, Kavita McLaughlin, Kerry A. Christie, Michael R.
Description	Author Affiliation: McLaughlin KA ( Division of Diabetes and Nutritional Sciences, Guy's Campus, King's College London, London SE1 1UL, United Kingdom); Gulati K ( Division of Diabetes and Nutritional Sciences, Guy's Campus, King's College London, London SE1 1UL, United Kingdom); Richardson CC ( Division of Diabetes and Nutritional Sciences, Guy's Campus, King's College London, London SE1 1UL, United Kingdom); Morgan D ( Division of Epidemiology, University of Leeds, Leeds LS2 9JT, United Kingdom.); Bodansky HJ ( Division of Epidemiology, University of Leeds, Leeds LS2 9JT, United Kingdom.); Feltbower RG ( Division of Epidemiology, University of Leeds, Leeds LS2 9JT, United Kingdom.); Christie MR ( Division of Diabetes and Nutritional Sciences, Guy's Campus, King's College London, London SE1 1UL, United Kingdom)
Abstract	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 IFN-Î³ and IL-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 characterized for Abs to IA-2 epitopes. T cell responses were detected to all peptides tested, but only IL-10 responses to 841-860 and 853-872 peptides were associated with DR4. Phenotyping by RT-PCR of FACS-sorted CD45RO(hi) T cells secreting IL-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 Abs: those to 841-860 peptide with Abs to juxtamembrane epitopes, which appear early in prediabetes, and those to peptide 853-872 with Abs to an epitope located in the 831-862 central region of the IA-2 tyrosine phosphatase domain. Abs 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.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1301902
Journal	The Journal of Immunology
Issue Number	9
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Autoantigens Immunology B-lymphocytes Diabetes Mellitus, Type 1 Epitopes Hla-dr4 Antigen Receptor-like Protein Tyrosine Phosphatases, Class 8 T-lymphocytes Adolescent Alleles Autoantibodies Metabolism Genetics Immunophenotyping Interleukin-10 Biosynthesis Peptides Phenotype Chemistry Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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