title: Ubiquitin-fusion degradation pathway: a new strategy for inducing CD8 cells specific for mycobacterial HSP65.
abstract: The ubiquitin-proteasome system (UPS) plays an indispensable role in inducing MHC class I-restricted CD8(+) T cells. In this study, we exploited UPS to induce CD8(+) T cells specific for mycobacterial HSP65 (mHSP65), one of the leading vaccine candidates against infection with Mycobacterium tuberculosis. A chimeric DNA termed pU-HSP65 encoding a fusion protein between murine ubiquitin and mHSP65 was constructed, and C57BL/6 (B6) mice were immunized with the DNA using gene gun bombardment. Mice immunized with the chimeric DNA acquired potent resistance against challenge with the syngeneic B16F1 melanoma cells transfected with the mHSP65 gene (HSP65/B16F1), compared with those immunized with DNA encoding only mHSP65. Splenocytes from the former group of mice showed a higher grade of cytotoxic activity against HSP65/B16F1 cells and contained a larger number of granzyme B- or IFN-gamma-producing CD8(+) T cells compared with those from the latter group of mice.
authors.affiliation: Department of Parasitology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Jianying
authors.initials: J
authors.lastname: Shen
authors.forename: Hajime
authors.initials: H
authors.lastname: Hisaeda
authors.forename: Bin
authors.initials: B
authors.lastname: Chou
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Yu
authors.forename: Liping
authors.initials: L
authors.lastname: Tu
authors.forename: Kunisuke
authors.initials: K
authors.lastname: Himeno
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology*; D002478:Cells, Cultured; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D025801:Ubiquitin / Q000235:genetics / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins