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

Abstract

Type 1 diabetes (T1D) is caused by T cell-mediated destruction of the pancreatic insulin-producing β 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 cy..