T-cell epitopes in type 1 diabetes.
Type 1 diabetes (TID) results from T-cell-mediated destruction of pancreatic b cells in genetically predisposed individuals. Autoreactive CD4(+) T helper cells and CD8(+) cytotoxic T lymphocytes (CTLs) recognize b-cell-derived peptides in the context of major histocompatibility complex class II and I molecules, respectively, in a process that terminates in b-cell death. Many peptide epitopes derived from b-cell proteins have been described for both humans and the nonobese diabetic (NOD) mouse, but their relative importance in disease pathogenesis is unclear. The significance of identifying key b-cell epitopes is underscored by a study showing that in the NOD mouse monitoring of a single population of b-cell-specific CTLs in the peripheral blood using a high-avidity analogue of the endogenous peptide may be used to accurately predict diabetes occurrence. Future studies focused on the discovery of immunodominant b-cell epitopes and their high-avidity analogues should have considerable implications for prediction and immunotherapy of TID.
Panagiotopoulos
Constadina
C
British Columbia's Children's Hospital, Department of Pathology and Laboratory Medicine, 4480 Oak Street, Room 2G11, Vancouver, British Columbia V6H 3V4, Canada.
Trudeau
Jacqueline D
JD
Tan
Rusung
R
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D007328:Insulin