title: Immunostimulatory activity of major membrane protein II from Mycobacterium tuberculosis.
abstract: Previously, we observed that both major membrane protein II of Mycobacterium leprae (MMP-ML) and its fusion with M. bovis BCG (BCG)-derived heat shock protein 70 (HSP70) (Fusion-ML) are immunogenic and that recombinant BCG secreting either of these proteins effectively inhibits the multiplication of M. leprae in mice. Here, we purified M. tuberculosis-derived major membrane protein II (MMP-MTB) and its fusion with HSP70 (Fusion-MTB) in a lipopolysaccharide-free condition and evaluated their immunostimulatory abilities. Both MMP-MTB and Fusion-MTB activated monocyte-derived dendritic cells (DC) in terms of phenotype and interleukin-12 (IL-12) production, but Fusion-MTB more efficiently activated them than MMP-MTB did. The IL-12 production was a consequence of the ligation of those recombinant proteins with Toll-like receptor 2. The M. tuberculosis-derived and M. leprae-derived recombinant proteins activated naïve T cells of both CD4 and CD8 subsets, but M. tuberculosis-derived proteins were superior to M. leprae-derived proteins and fusion proteins were superior to MMP, regardless of the origin of the protein. Memory-type CD4(+) T cells obtained from BCG-vaccinated healthy individuals seem to be primed with MMP-MTB by the vaccination, and both M. tuberculosis-derived recombinant proteins produced perforin-producing CD8(+) T cells from memory-type CD8(+) T cells. Further, infection of DC and macrophages with M. tuberculosis H37Ra and H37Rv induced the expression of MMP on their surface. These results indicate that M. tuberculosis-derived MMP, as a sole protein or as part of a fusion protein, may be useful for developing new vaccinating agents against tuberculosis.
authors.affiliation: Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Tsukamoto
authors.forename: Masumi
authors.initials: M
authors.lastname: Endoh
authors.forename: Tetsu
authors.initials: T
authors.lastname: Mukai
authors.forename: Yumi
authors.initials: Y
authors.lastname: Maeda
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tamura
authors.forename: Masanori
authors.initials: M
authors.lastname: Kai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Makino
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002675:Child, Preschool; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D051195:Toll-Like Receptor 2; C500901:major membrane protein II, Mycobacterium leprae; D018664:Interleukin-12