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Infection and Immunity, December 2001, p. 7349-7355, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7349-7355.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mycobacterium tuberculosis Chaperonin 60.1 Is a More Potent Cytokine Stimulator than Chaperonin 60.2 (Hsp 65) and Contains a CD14-Binding Domain

Jo C. Lewthwaite,1 Anthony R. M. Coates,2 Peter Tormay,2 Mahavir Singh,3 Paolo Mascagni,4 Stephen Poole,5 Michael Roberts,2 Lindsay Sharp,1 and Brian Henderson1,*

Cellular Microbiology Research Group, Eastman Dental Institute, University College London,1 and Department of Medical Microbiology, St. George's Hospital Medical School, Tooting,2 London, and Division of Endocrinology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire,5 United Kingdom; Department of Biochemistry, TU-Braunschweig, c/o GBF, and Lionex GmbH, Braunschweig, Germany3; and Italfarmaco SpA, Centro Richerche, Cinisello B (MI), Italy4

Received 14 March 2001/Returned for modification 12 April 2001/Accepted 9 July 2001

Much attention has focused on the Mycobacterium tuberculosis molecular chaperone chaperonin (Cpn) 60.2 (Hsp 65) in the pathology of tuberculosis because of its immunogenicity and ability to directly activate human monocytes and vascular endothelial cells. However, M. tuberculosis is one of a small group of bacteria that contain multiple genes encoding Cpn 60 proteins. We have 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 synthesis than is Cpn 60.2. This is in spite of 76% amino acid sequence similarity between the two mycobacterial chaperonins. The M. tuberculosis Cpn 60.2 protein activates human peripheral blood mononuclear cells by a CD14-independent mechanism, whereas Cpn 60.1 is partially CD14 dependent and contains a peptide sequence whose actions are blocked by anti-CD14 monoclonal antibodies. The cytokine-inducing activity of both chaperonins is extremely resistant to heat. Cpn 60.1 may be an important virulence factor in tuberculosis, able to activate cells by diverse receptor-driven mechanisms.

* Corresponding author. Mailing address: Cellular Microbiology Research Group, Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, United Kingdom. Phone and fax: 44 (0) 20 7915 1190. E-mail: B.Henderson{at}eastman.ucl.ac.uk.

Infection and Immunity, December 2001, p. 7349-7355, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7349-7355.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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