Open AccessVaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein.
Author(s) -
Dana Elias,
Tamara Reshef,
Ohad S. Birk,
Ruurd van der Zee,
Michael D. Walker,
Irun R. Cohen
Publication year - 1991
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.88.8.3088
Subject(s) - insulitis , epitope , nod mice , heat shock protein , nod , immunology , t cell , diabetes mellitus , immune system , autoimmunity , biology , vaccination , insulin , pancreatic islets , antigen , medicine , endocrinology , islet , biochemistry , gene
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.