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Publication : Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein.

First Author  Elias D Year  1991
Journal  Proc Natl Acad Sci U S A Volume  88
Issue  8 Pages  3088-91
PubMed ID  1707531 Mgi Jnum  J:14788
Mgi Id  MGI:62949 Doi  10.1073/pnas.88.8.3088
Citation  Elias D, et al. (1991) Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein. Proc Natl Acad Sci U S A 88(8):3088-91
abstractText  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.
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