M. tuberculosis reactive CD4+ T cell clones were established from a BCG vaccinated donor and tested for proliferative responses against complex mycobacterial antigens like M. tuberculosis, M. leprae, and PPD, as well as the recombinant M. tuberculosis HSP70 and HSP65 antigens from both M. tuberculosis and M. leprae. This screening permitted the identification of T cell clones specifically recognizing the mycobacterial HSP70 or HSP65 antigen. All HSP65 reactive T cell clones were cross-reactive for M. tuberculosis and M. leprae, whereas three HSP70 reactive T cell clones only recognized M. tuberculosis. In addition, HLA typing and blocking experiments with anti-HLA antibodies revealed that antigen presentation to all M. tuberculosis reactive T cell clones was restricted by HLA-DR3 molecules. We have thereby demonstrated the presence of human T cell specificities directed against the mycobacterial HSP70 antigen that are able to discriminate between M. tuberculosis and M. leprae.
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