Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein.
Insulin-dependent diabetes mellitus is caused by autoimmune destruction of the insulin-producing beta cells resident in the pancreatic islets. We recently discovered that the pathogenesis of diabetes in NOD strain mice was associated with T-cell reactivity to an antigen cross-reactive with a mycobacterial 65-kDa heat shock protein. To identify peptide epitopes critical to the insulin-dependent diabetes mellitus of NOD mice, we studied the specificities of helper T-cell clones capable of causing hyperglycemia and diabetes. We now report the identification of a functionally important peptide within the sequence of the human variant of the 65-kDa heat shock protein molecule. T-cell clones recognizing this peptide mediate insulitis and hyperglycemia. Alternatively, the T cells can be attenuated and used as therapeutic T-cell vaccines to abort the diabetogenic process. Moreover, administration of the peptide itself to NOD mice can also down-regulate immunity to the 65-kDa heat shock protein and prevent the development of diabetes. Thus, T-cell vaccination and specific peptide therapy are feasible in spontaneous autoimmune diabetes.
Elias
D
D
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Reshef
T
T
Birk
O S
OS
van der Zee
R
R
Walker
M D
MD
Cohen
I R
IR
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control; D002999:Clone Cells; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D000939:Epitopes; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007116:Immunization, Passive; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D000939:Epitopes; D006360:Heat-Shock Proteins; D010455:Peptides