Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library

FS Wong, J Karttunen, C Dumont, L Wen, I Visintin… - Nature medicine, 1999 - nature.com
FS Wong, J Karttunen, C Dumont, L Wen, I Visintin, IM Pilip, N Shastri, EG Pamer
Nature medicine, 1999nature.com
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic β cells
are destroyed at an early age by an immune process that involves both CD4 and CD8 T
lymphocytes. The identification of autoantigens in diabetes is very important for the design of
antigen-specific immunotherapy. By screening a pancreatic islet cDNA library, we have
identified the autoantigen recognized by highly pathogenic CD8 T cells in the non-obese
diabetic mouse, one of the best animal models for human diabetes. This is the first …
Abstract
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic β cells are destroyed at an early age by an immune process that involves both CD4 and CD8 T lymphocytes. The identification of autoantigens in diabetes is very important for the design of antigen-specific immunotherapy. By screening a pancreatic islet cDNA library, we have identified the autoantigen recognized by highly pathogenic CD8 T cells in the non-obese diabetic mouse, one of the best animal models for human diabetes. This is the first identification, to our knowledge, of a CD8 T-cell epitope in an autoimmune disease. The peptide recognized by the cells is in the same region of the insulin B chain as the epitope recognized by previously isolated pathogenic CD4 T cells. This has very important implications for the potential use of insulin in preventative therapy.
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