Mycobacterium tuberculosis chaperonin 60.1 is a more potent cytokine stimulator than chaperonin 60.2 (Hsp 65) and contains a CD14-binding domain

Much attention has focused on the Mycobacterium tuberculosis molecular chap erone chaperonin (Cpn) 60.2 (Hsp 65) in the pathology of tuberculosis becau se of its immunogenicity and ability to directly activate human monocytes a nd vascular endothelial cells. However, M. tuberculosis is one of a small g roup of bacteria that contain multiple genes encoding Cpn 60 proteins. We h ave now cloned and expressed both M. tuberculosis proteins and report that the novel chaperonin 60, Cpn 60.1, is a more potent inducer of cytokine syn thesis than is Cpn 60.2. This is in spite of 76% amino acid sequence simila rity between the two mycobacterial chaperonins. The M. tuberculosis Cpn 60. 2 protein activates human peripheral blood mononuclear cells by a CD14-inde pendent mechanism, whereas Cpn 60.1 is partially CD14 dependent and contain s a peptide sequence whose actions are blocked by anti-CD14 monoclonal anti bodies. The cytokine-inducing activity of both chaperonins is extremely res istant to heat. Cpn 60.1 may be an important virulence factor in tuberculos is, able to activate cells by diverse receptor-driven mechanisms.