H2-M3-restricted CD8⁺ T cells induced by peptide-pulsed dendritic cells confer protection against Mycobacterium tuberculosis

One of the oligopolymorphic MHC class Ib molecules, H2-M3, presents N-formylated peptides derived from bacteria. In this study, we tested the ability of an H2-M3-binding pepiide, TB2, to induce protection in C57BL/6 mice against Mycobacterium tuberculosis. Immunization with bone marrow-derived dendritic cell (BMDC) pulsed with TB2 or a MI-IC class la-binding peptide, MDPT64_190-198 elicited an expansion of Ag-specific CD8⁺ T cells in the spleen and the lung. The number of TB2-specific CD8⁺ T cells reached a peak on day 6, contracted with kinetics similar to MPT64 _190-198-specific CD8⁺ T cells and was maintained at an appreciable level for at least 60 days. The TB2-specific CD8⁺ T cells produced less effector cytokines but have stronger cytotoxic activity than MPT64_190-198-specific CD8⁺ T cells. Mice immunized with TB2-pulsed BMDC as well as those with MPT64_190-198-pulsed BMDC showed significant protection against an intratracheal challenge with M. tuberculosis H37Rv. However, histopathology of the lung in mice immunized with TB2-pulsed BMDC was different from mice immunized with MPT64_190-198-specific BMDC. Our results suggest that immunization with BMDC pulsed with MHC class 1b-restricted peptides would be a useful vaccination strategy against M. tuberculosis.