Sequence and structural homologies between M. tuberculosis chaperonin 10 and the MHC class I/II peptide binding cleft.

The peptide corresponding to the C-terminal half of M.tuberculosis hsp10 was synthesised based on the prediction that it might represent an independent structural region of the protein. This hypothesis was confirmed by aggregation and CD studies using this peptide and longer sequences of the protein. The peptide shares about 40-50% sequence homology with alpha 2 and beta 1 chains of MHC class I and II antigens. This and the CD results which indicated that the peptide at acidic pHs folds into an anti-parallel beta-sheet were used to generate a 3D model which has the same "W" fold contained in the MHC peptide binding groove. These data suggest that the hypothesis of molecular mimicry proposed to be one of the mechanisms which triggers autoimmune diseases may be extended to hsp10 proteins. Furthermore the suggested evolutionary relationship between hsp's and MHC antigens may find support from these data.