Epitopes described in "The A-chain of insulin is a hot-spot for CD4+ T cell epitopes in human type 1 diabetes."

Article Authors:S I Mannering; S H Pang; N A Williamson; G Naselli; E C Reynolds; N M O'Brien-Simpson; A W Purcell; L C Harrison
Article Title:The A-chain of insulin is a hot-spot for CD4+ T cell epitopes in human type 1 diabetes.
Reference Detail
Reference ID:1014210
Abstract:Type 1 diabetes (T1D) is caused by T cell-mediated destruction of the pancreatic insulin-producing beta cells. While the role of CD4(+) T cells in the pathogenesis of T1D is accepted widely, the epitopes recognized by pathogenic human CD4(+) T cells remain poorly defined. None the less, responses to the N-terminal region of the insulin A-chain have been described. Human CD4(+) T cells from the pancreatic lymph nodes of subjects with T1D respond to the first 15 amino acids of the insulin A-chain. We identified a human leucocyte antigen-DR4-restricted epitope comprising the first 13 amino acids of the insulin A-chain (A1-13), dependent upon generation of a vicinal disulphide bond between adjacent cysteines (A6-A7). Here we describe the analysis of a CD4(+) T cell clone, isolated from a subject with T1D, which recognizes a new HLR-DR4-restricted epitope (KRGIVEQCCTSICS) that overlaps the insulin A1-13 epitope. This is a novel epitope, because the clone responds to proinsulin but not to insulin, T cell recognition requires the last two residues of the C-peptide (Lys, Arg) and recognition does not depend upon a vicinal disulphide bond between the A6 and A7 cysteines. The finding of a further CD4(+) T cell epitope in the N-terminal A-chain region of human insulin underscores the importance of this region as a target of CD4(+) T cell responses in human T1D.
Affiliations:Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Australia. smannering@svi.edu.au.
Reference Type:Literature
PubMed ID:19292763
Journal:Clin Exp Immunol
Journal Volume:156
Article Pages:226-31
Journal ISSN:0009-9104
Article Chemical List:C-Peptide;Epitopes, T-Lymphocyte;HLA-DR4 Antigen;Insulin;Receptors, Antigen, T-Cell;Proinsulin;Cysteine
Article MeSH List:Antigen Presentation; C-Peptide(chemistry); CD4-Positive T-Lymphocytes(immunology); Cysteine(chemistry); Diabetes Mellitus, Type 1(immunology); Epitope Mapping; Epitopes, T-Lymphocyte(chemistry; immunology); HLA-DR4 Antigen(immunology); Humans; Insulin(chemistry; immunology); Proinsulin(chemistry; immunology); Receptors, Antigen, T-Cell(immunology)
Curation Last Updated:2015-06-05 01:35:21