Os. Birk et al., NOD MOUSE DIABETES - THE UBIQUITOUS MOUSE HSP60 IS A BETA-CELL TARGETANTIGEN OF AUTOIMMUNE T-CELLS, Journal of autoimmunity, 9(2), 1996, pp. 159-166
In the NOD mouse, the onset of beta-cell destruction is associated wit
h 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 prio
r immunization. Therefore, it has been suggested that the anti-hsp60 T
cells involved in the autoimmune diabetes of NOD mice might reflect m
olecular mimicry between MT-hsp60 and a beta-cell tissue specific mole
cule sharing similar T cell epitopes, the p277 peptide of hsp60 in par
ticular. We cloned and expressed the mouse hsp60 cDNA from a beta-cell
tumour. This mouse beta-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 whi
ch 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 a
utoreactive, and are targeted at the mouse beta-cell hsp60, which is n
ot tissue specific. These findings raise the question of how a non-tis
sue specific molecule may be a target of a tissue-specific autoimmune
disease. (C) 1996 Academic Press Limited