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Infect. Immun. doi:10.1128/IAI.00307-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Bacterial protein secretion is required for priming of CD8⁺ T cells specific for the Mycobacterium tuberculosis antigen CFP10

Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Program in Immunology, Harvard Medical School, and Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA

^* To whom correspondence should be addressed. Email: sbehar{at}rics.bwh.harvard.edu.

	Abstract

Mycobacterium tuberculosis (Mtb) infection elicits antigen-specific CD8+ T cells that are required to control disease. It is unknown how the class I MHC pathway samples mycobacterial antigens. CFP10 and ESAT6 are important virulence factors secreted by Mtb and are immunodominant targets of the human and murine T cell response. Here, we test the hypothesis that CFP10 secretion by Mtb is required for priming of CD8+ T cells in vivo. Our results reveal an explicit dependence upon bacterial secretion of the CFP10 antigen for the induction of antigen-specific CD8+ T cells in vivo. By using well-defined Mtb mutants and carefully controlling for virulence, we show that ESX-1 function is required for priming of CD8⁺ T cells specific for CFP10. CD4⁺ and CD8⁺ T cell responses to mycobacterial antigens secreted independently of ESX-1 were unaffected, suggesting that ESX-1 dependent phagosomal escape is not required for CD8+ T cell priming during infection. We propose that the over-representation of secreted proteins as dominant targets of the CD8+ T cell response during Mtb infection is a consequence of their preferential sampling by the class I MHC pathway. The implications of these findings should be considered in all models of antigen presentation during Mtb infection and in vaccine development.