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Identification of HLA-restricted cytotoxic T cell epitopes of Mycobcaterium tuberculosis for developing epitope vaccines

Research Project

Project/Area Number 13670268
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

KOIDE Yukio  Hamamatsu University School of medicine, Department of Microbiology and Immunology, Professor, 医学部, 教授 (30126809)

Co-Investigator(Kenkyū-buntansha) UCHIJIMA Masato  Hamamatsu University School of Medicine, Department of Microbiology and Immunology, Assistant Professor, 医学部, 助手 (20252174)
NAGATA Toshi  Hamamatsu University School of Medicine, Department of Microbiology and Immunology, Associate Professor, 医学部, 助教授 (90275024)
OHARA Naoya  Nagasaki University Graduate School of Biomedical Sciences, Course of Medical and Dental Sciences, Division of Microbiology and Oral Infection, Associate Professor, 歯学部, 助教授 (70223930)
AOSHI Taiki  Hamamatsu University School of Medicine, Department of Microbiology and Immunology, Assistant Professor, 医学部, 助手 (10324344)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsMycobacterium tuberculosis / Epitopes / DNA vaccines / Algorism / T cells
Research Abstract

The best vaccine available against tuberculosis (TB), BCG, gives variable protective efficacy. Therefore, there remains an urgent need for an improved vaccine. DNA vaccine is capable of inducing strong cellular immunity involved in the protection against TB. Therefore, DNA vaccine is a candidate to induce more effective protective immunity against TB. We, previously, observed that DNA vaccine expressing a single epitope is more potent in the induction of protective immunity than that encoding whole molecules. In this project, therefore, we tried to identify T-cell epitopes of M. tuberculosis antigens. As we demonstrated that MPB51 antigen is one of major protective antigens of M. tuberculosis. We attempted T-cell epitopes of MPB51 employing overlapping peptide library and computer algorism. Then, we found I-A^b-restricted CD4 T-cell epitopes in amino acid residues 171-190 and 191-210 and an H-2^b-restricted CD8 T-cell in residues 21-40. Furthermore, employing H-2 class I knockout, HLA-A^*0201-transgenic mice, we found an HLA-A^*0201-restricted CD8^+T-cell epitope of MPB51.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Yutaro Nakamura: "Induction of protective immunity against an intracellular bacterium using dendritic cells retrovirally transduced with a minigene encoding a CTL epitope"Infection and Immunity. 71. 1748-1754 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroshi Uchiyama: "Endosomal/lysosomal targeting of a single helper T-cell epitope of an intracellular bacterium by DNA immunization induces a specific T-cell subset and partial protective immunity in vivo"FEBS Microbiology Letters. 216. 91-97 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshi Nagata: "Immunization with plasmid DNA encoding MHC class II binding peptide/CLIP-replaced invariant chain (Ii) induces specific helper T cells in vivo the assessment of Ii p31 and p41 isoforms as vehicles for immunization"Vaccine. 20. 105-114 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshi Nagata: "Induction of protective immunity to Listeria monocytogenes by immunization with plasmid DNA expressing a helper T-cell epitope that replaces the class II-associated invariant chain peptide of the invariant chain"Infection and Immunity. 70. 2676-2680 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ken Sugimoto: "Curcumin ameliorates trinitrobenzene sulfonic acid (TNBS) -induced colitis in mice"Gastroenterology. 123. 1912-1922 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Baoxing Li: "Pretreatment of recipients with mitomycin-C-treated dendritic cells induces significant prolongation of cardiac allograft survival in mice"Transplantation Proceedings. 34. 3426-3428 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 小出幸夫: "血液・免疫・腫瘍(DNAワクチンによる感染防御)"メディカルレビュー社. 372-384 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamada T., et al.: "Protective CTL responses induced by DNA immunization against immunodominant and subdominant epitopes of Listeria mono-cytogenes are noncompetitive"Infect. Immun.. 69(5). 3427-3430 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokota N., et al.: "Identification of differentially expressed genes in rat hippocampus after transient global cerebral ischemia using subtractive cDNA cloning based on PCR"Stroke. 32. 168-174 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida A., et al.: "Protective CTL response is induced in the absence of CD4^+ T cells and IFN-γ by gene gun DNA vaccination with a minigene enco-ding a CTL epitope of Listeria mono-cytogenes"Vaccine. 19(30). 4297-4306 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uchijima M., et al.: "Identification of immuno- stimulatory DNA-induced genes by suppression subtractive hybridization"Biochem. Biophys. Res. Commun.. 286. 688-691 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagata T., et al.: "Immunization with plasmid DNA encoding MHC class II binding peptide/CLIP-replaced invariant chain (Ii) induces specific helper T cells in vivo the assessment of Ii p31 and p41 isoforms as vehicles for immunization"Vaccine. 20. 105-114 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagata T., et al.: "Induction of protective immunity to Listeria mono- cytogenes by immunization with plasmid DNA expressing a helper T-cell epitope that replaces the class II-associated invariant chain peptide of the invariant chain"Infect Immun.. 70(5). 2676-2680 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugimoto K, et al.: "Curcumin ameliorates trinitrobenzene sulfonic acid (TNBS) induced colitis in mice"Gastroenterology. 123. 1912-1922 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li B, Koide Y, Uchijima M, Ohtawara Y, Fujita K: "Pretreatment of recipients with mitomycin-C-treated dendritic cells induces significant prolongation of cardiac allograft survival in mice"Transplant. Proc.. 34(8). 3426-3428 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uchiyama H., et al.: "Endosomal/lysosomal targeting of a single helper T-cell epitope of an intracellular bacterium by DNA immunization induces a specific T-cell subset and partial protective immunity in vivo"FEMS Microbiol. Lett.. 216. 91-97 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uenoyama, S, et al.: "Improvement of intestinal motility using S-methylisothiourea sulfare in a caine postoperative ileus model"Am J Surg. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tozawa K, et al.: "Evidence for the critical role of interleukin-12 but not interferon-g in the pathogenesis of experimental colitis in mice"J Gastroenterol Hepatol. 18(5). 578-587 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura Y, et al.: "Induction of protective immunity against an intracellular bacterium using dendritic cells retrovirally transduced with a minigene encoding a CTL epitope"Infect Immun. 71. 1784-1754 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yutaro Nakamura: "Induction of protective immunity against an intracellular bacterium using dendritic cells retrovirally transduced with a minigene encoding a CTL epitope"Infection and Immunity. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiroshi Uchiyama: "Endosomal/lysosomal targeting of a single helper T-cell epitope of an intracellular bacterium by DNA immunization induces a specific T-cell subset and partial protective immunity in vivo"FEBS Microbiology Letters. 216. 91-97 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toshi Nagata: "Immunization with plasmid DNA encoding MHC class II binding peptide/CLIP-replaced invariant chain (Ii) induces specific helper T cells in vivo : the assessment of Ii p31 and p41 isoforms as vehicles for immunization"Vaccine. 20. 105-114 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toshi Nagata: "Induction of protective immunity to Listeria monocytogenes by immunization with plasmid DNA expressing a helper T-cell epitope that replaces the class II-associated invariant chain peptide of the invariant chain"Infection and Immunity. 70. 2676-2680 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ken Sugimoto: "Curcumin ameliorates trinitrobenzene sulfonic acid (TNBS) -induced colitis in mice"Gastroenterology. 123. 1912-1922 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Baoxing Li: "Pretreatment of recipients with mitomycin-C-treated dendritic cells induces significant prolongation of cardiac allograft survival in mice"Transplantation Proceedings. 34. 3426-3428 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小出幸夫: "血液・免疫・腫瘍(DNAワクチンによる感染防御)"メディカルレビュー社. 372-384 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toshi Nagata: "Induction of protective immunity to Listeria monocytogenes by immunization with plasmid DNA expressing a helper T-cell epitope that replaces the class II-associated invariant chain peptide of the invariant chain"Infection and Immunity. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masato Uchijima: "Identification of immunostimulatory DNA-induced genes by suppression subtractive hybridization"Biochem. Biophys. Res. Commun.. 286. 688-691 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Toshi Nagata: "Immunization with plasmid DNA encoding MHC class II binding peptide/CLIP-replaced invariant chain (Ii) induces specific helper T cells in vivo : the assessment of Ii p31 and p41 isoforms as vehicles for immunization"Vaccine. 20. 105-114 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Atsushi Yoshida: "Protective CTL response is induced in the absence of CD4^+ T cells and IFN-γ by gene gun DNA vaccination with a minigene encoding a CTL epitope of Listeria monocytogenes"Vaccine. 19. 4297-4306 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takashi Yamada: "Protective CTL responses induced by DNA immunization against immunodominant and subdominant epitopes of Listeria monocytogenes are noncompetitive"Infection and Immunity. 69. 3427-3430 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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