NOD mouse diabetes: The ubiquitous mouse hsp60 is a β-cell target antigen of autoimmune T cells

Ohad S. Birk, Dana Elias, Alona S. Weiss, Ada Rosen, Ruurd Van-Der Zee, Michael D. Walker, Irun R. Cohen

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


In the NOD mouse, the onset of β-cell destruction is associated with spontaneous development of T-lymphocytes reactive to members of the 60 kDa heat shock protein (hsp60) family, including the Mycobacterial (MT) and the human (H) hsp60 molecules. Diabetes in the NOD mouse is a spontaneous tissue-specific autoimmune disease occurring without prior immunization. Therefore, it has been suggested that the anti-hsp60 T cells involved in the autoimmune diabetes of NOD mice might reflect molecular mimicry between MT-hsp60 and a β-cell tissue specific molecule sharing similar T cell epitopes, the p277 peptide of hsp60 in particular. We cloned and expressed the mouse hsp60 cDNA from a β-cell tumour. This mouse β-cell hsp60 cDNA was found to be identical in sequence to the hsp60 of mouse fibroblasts. We further report that NOD spleen cells and an NOD diabetogenic T cell clone C9 responded to the recombinant mouse hsp60 and to its peptide M-p277 to the same extent as to H-hsp60 and H-p277. Splenocytes of mice of other strains did not respond to p277. Moreover, treatment of 3 month old NOD mice with the non-modified self M-p277 peptide was as efficient as H-p277, from which it differs in one amino acid, in halting progression of the disease. Thus, anti-H-p277 T cells modulating diabetes in the NOD mouse are autoreactive, and are targeted at the mouse β-cell hsp60, which is not tissue specific. These findings raise the question of how a non-tissue specific molecule may be a target of a tissue-specific autoimmune disease.

Original languageEnglish
Pages (from-to)159-166
Number of pages8
JournalJournal of Autoimmunity
Issue number2
StatePublished - 1 Jan 1996
Externally publishedYes


  • Autoimmunity
  • Diabetes mellitus
  • hsp60

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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