Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library.
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta 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.
Wong
F S
FS
Section of Immunobiology, Yale School of Medicine, 310 Cedar Street, New Haven, Connecticut 06520-8011, USA. susan.wong@yale.edu
Karttunen
J
J
Dumont
C
C
Wen
L
L
Visintin
I
I
Pilip
I M
IM
Shastri
N
N
Pamer
E G
EG
Janeway
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019556:COS Cells; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D003001:Cloning, Molecular; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015723:Gene Library; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007328:Insulin / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D009928:Organ Specificity; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D007328:Insulin; D010455:Peptides; D007371:Interferon-gamma