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The Journal of Immunology, 2007, 178: 3806-3813.
Copyright © 2007 by The American Association of Immunologists, Inc.

H2-M3-Restricted CD8+ T Cells Induced by Peptide-Pulsed Dendritic Cells Confer Protection against Mycobacterium tuberculosis1

Takehiko Doi*,{dagger}, Hisakata Yamada2,*, Toshiki Yajima*, Worawidh Wajjwalku{ddagger}, Toshiro Hara{dagger} and Yasunobu Yoshikai*

* Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; {dagger} Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka, Japan; and {ddagger} Department of Pathology, Faculty of Veterinary Medicine, Kasetsart University, Nakhonpathom, Thailand

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 peptide, TB2, to induce protection in C57BL/6 mice against Mycobacterium tuberculosis. Immunization with bone marrow-derived dendritic cell (BMDC) pulsed with TB2 or a MHC class Ia-binding peptide, MPT64190–198 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 MPT64190–198-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 MPT64190–198-specific CD8+ T cells. Mice immunized with TB2-pulsed BMDC as well as those with MPT64190–198-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 MPT64190–198-pulsed BMDC. Our results suggest that immunization with BMDC pulsed with MHC class Ib-restricted peptides would be a useful vaccination strategy against M. tuberculosis.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported in part by the Program of Founding Research Centers for Emerging and Re-emerging Infectious Diseases launched as a project commissioned by the Ministry of Education, Culture, Sports, Science and Technology, Japan, by a Grant-in-Aid for Japan Society for Promotion of Science, and grants from the Japanese Ministry of Education, Science, and Culture (to Y.Y.).

2 Address correspondence and reprint requests to Dr. Hisakata Yamada, Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. E-mail address: hisaky{at}hotmail.com

3 Abbreviations used in this paper: BCG, Mycobacterium bovis bacillus Calmette-Guérin; DC, dendritic cell; BMDC, bone marrow-derived DC; MFI, mean fluorescent intensity.




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