Heat-shock protein 65 as a beta cell antigen of insulin-dependent diabetes.
The primary beta-cell antigen of insulin-dependent diabetes is thought to be a protein with a molecular weight of approximately 64 kD. Hyperthermic incubation and cytokines such as interleukin 1 beta, gamma interferon, and tumour necrosis factor induce synthesis of 64 kD protein by insulinoma cells. By western blot techniques, cross-reactivity was found between this 64 kD protein and monoclonal antibodies directed against Mycobacterium tuberculosis heat-shock protein 65, but not with antibodies directed against a similar epitope of M leprae heat-shock protein 65. Binding of M tuberculosis heat-shock protein 65 antibodies to interleukin-1 beta-treated cells was inhibited by prior addition of serum from insulin-dependent diabetic patients which contained antibodies to 64 kD beta-cell antigen. It is suggested that heat-shock protein 65 may be the 64 kD beta-cell antigen and that autoreactivity to an epitope of heat-shock protein 65 may confer susceptibility to insulin-dependent diabetes mellitus.
Jones
D B
DB
Department of Medicine, Western General Hospital, Edinburgh, UK.
Hunter
N R
NR
Duff
G W
GW
D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis*; D001345:Autoradiography; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000032:analysis* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007340:Insulinoma / Q000188:drug therapy / Q000276:immunology; D007375:Interleukin-1 / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology; D051381:Rats; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006360:Heat-Shock Proteins; D007375:Interleukin-1