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Research of T cell immunity to Epstein-Barr virus latent membrane protein 1.

Research Project

Project/Area Number 15590429
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionAichi Cancer Center

Principal Investigator

KUZUSHIMA Kiyotaka  Aichi Cancer Center, Division of Immunology, Chief, 腫瘍免疫学部, 部長 (30311442)

Co-Investigator(Kenkyū-buntansha) 出町 文子  愛知県がんセンター, 腫瘍免疫学部, リサーチレジデント
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsEpstein-Barr virus / cytotoxic T lymphocyte / proteasome / HLA / short hairpin RNA / Epstein-Barr Virus / 細胞傷害性Tリンパ球
Research Abstract

1.Epstein-Barr Virus(EBV) latent membrane protein(LMP)1,LMP2 and EBNA1 antigens are expressed in EBV-positive malignancies and candidate molecules recognized by cytotoxic T lymphocytes(CTL). To efficiently induce CTL responses to them, we applied antigen presenting cells transduced with in vitro transcribed mRNA coding each molecules to stimulate CD8+ T cells obtained from healthy donors. An HLA-A^*0206-restricted LMP1-specific CTL clone was established. The T cell clone exhibited MHC-restricted cytotoxicity to cell lines derived from EBV-positive NK lymphoma. I also established HLA-Cw^*0303-restricted EBNA1-specific CTL clone which inhibited growth of HLA-Cw^*0303-positive EBV-infected B-lymphoblastoid cell lines(LCLs). Amino acid sequences of the CTL epitopes were identified using truncated mutants of the target genes and synthetic peptides.
2.An HLA-A^*2402-restricted LMP2-derived epitope whose amino acid sequence, IYVLVMLVL, had been identified by the head investigator (Blood.,2003). The epitope was presented on LCLs but not on fibroblast cells. Since IFN-γ induced the epitope presentation, I investigated the roles of subunits of so called immunoproteasome. For the sake, retrovirus vectors expressing short hairpin RNA to inhibit expression of β1i,β5i and PA28α were produced and infected to HLA^*A2402-positive LCLs. The reduced protein expression was confirmed by Western blotting. Presentation of the epitope determined by ELISPOT assay using the epitope-spepcific CTL clone, was decreased on LCLs, where either β1i,β5i or PA28α was knocked out.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (29 results)

All 2005 2004 2003 Other

All Journal Article (26 results) Publications (3 results)

  • [Journal Article] Differences between T Cell-Type and Natural Killer Cell-Type Chronic Active Epstein-Barr Virus Infection.2005

    • Author(s)
      Kimura H
    • Journal Title

      J.Infect.Dis. 191(4)

      Pages: 531-539

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Retroviral vector backbone immunogenicity : identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences.2005

    • Author(s)
      Kondo E
    • Journal Title

      Gene Ther. 12(3)

      Pages: 252-258

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differences between T Cell-Type and Natural Killer Cell-Type Chronic Active Epstein-Barr Virus Infection.2005

    • Author(s)
      Kimura H, Hoshino Y, Hara S, Sugaya N, Kawada J, Shibata Y, Kojima S, Nagasaka T, Kuzushima K, Morishima T.
    • Journal Title

      J.Infect.Dis. 191(4)

      Pages: 531-539

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Retroviral vector backbone immunogenicity : identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences.2005

    • Author(s)
      Kondo E, Akatsuka Y, Nawa A, Kuzushima K, Tsujimura K, Tanimoto M, Kodera Y, Morishima Y, Kuzuya K, Takahashi T.
    • Journal Title

      Gene Ther. 12(3)

      Pages: 252-258

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Quantitative analysis of Epstein-Bart virus (EBV)-specific CD8+ T cells in patients with chronic active EBV infection.2004

    • Author(s)
      Sugaya N.
    • Journal Title

      J.Infect.Dis. 190

      Pages: 985-988

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A*2402-restricted cytotoxic T-lymphocyte responses.2004

    • Author(s)
      Tajima K.
    • Journal Title

      Tissue Antigens 64

      Pages: 650-659

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interferon-γ differentially regulates susceptibility of lung cancer cells to telomerase-specific cytotoxic T lymphocytes.2004

    • Author(s)
      Tajima K.
    • Journal Title

      Int.J.Cancer 110

      Pages: 403-412

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reconstitution of HLA-A*2402-restricted cytomegalovirus-specific T-cells following stem cell transplantation.2004

    • Author(s)
      Gondo H.
    • Journal Title

      Int.J.Hematol. 80(5)

      Pages: 441-448

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Analysis of HLA-A24-restricted CMVpp65 peptide-specific CTL with HLA-A*2402-CMVpp65 tetramer.2004

    • Author(s)
      Akiyama Y
    • Journal Title

      Immunol Lett. 95(2)

      Pages: 199-205

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expansion of human CMV-specific cytotoxic T lymphocytes to a clinical scale : a simple culture system using tetrameric HLA-peptide complexes.2004

    • Author(s)
      Watanabe N
    • Journal Title

      Cytotherapy 6(5)

      Pages: 514-522

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Quantitative analysis of Epstein-Barr virus(EBV)-specific CD8^+ T cells in chronic active EBV infection.2004

    • Author(s)
      Sugaya, N., Kimura, H., Kara, S., Hoshino, Y., Kojima, S., Morishima, T., Tsurumi, T., Kuzushima, K.
    • Journal Title

      J.Infect.Dis. 190(5)

      Pages: 985-988

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interferon-y differentially regulates susceptibility of lung cancer cells to telomerase-specific cytotoxic T lymphocytes.2004

    • Author(s)
      Tajima, K., Ito, Y., Demachi, A., Nishida, K., Akatsuka, Y., Tsujimura, K., Hida, T., Morishima, Y., Kuwano, H., Mitsudomi, T., Takahashi, T., Kuzushima, K.
    • Journal Title

      Int.J.Cancer 110(3)

      Pages: 403-412

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A^*2402-restricted cytotoxic T-lymphocyte responses.2004

    • Author(s)
      Tajima K, Demachi A, Ito Y, Nishida K, Akatsuka Y, Tsujimura K, Kuwano H, Mitsudomi T, Takahashi T, Kuzushima K.
    • Journal Title

      Tissue Antigens. 64(6)

      Pages: 650-659

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles.2004

    • Author(s)
      Kondo, E., Akatsuka, Y., Kuzushima, K..Tsujimura, K., Asakura, S., Tajima, K., Kagami, Y., Kodera, Y., Tanimoto, M., Morishima, Y., Takahashi, T.
    • Journal Title

      2004.Blood 103

      Pages: 630-638

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reconstitution of HLA-A^*2402-restricted cytomegalovirus-specific T-cells following stem cell transplantation.2004

    • Author(s)
      Gondo H, Himeji D, Kamezaki K, Numata A, Tanimoto T, Takase K, Aoki K, Henzan H, Nagafuji K, Miyamoto T, Ishikawa F, Shimoda K, Inaba S, Tsukamoto H, Horiuchi T, Nakashima H, Otsuka T, Kato K, Kuroiwa M, Higuchi M, Shibuya T, Kamimura T, Kuzushima K, Tsurumi T, Kanda Y, Harada M.
    • Journal Title

      Int.J.Hematol. 80(5)

      Pages: 441-448

    • NAID

      10014089304

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Analysis of HLA-A24-restricted CMVpp65 peptide-specific CTL with HLA-A^*2402-CMVpp65 tetramer.2004

    • Author(s)
      Akiyama Y, Kuzushima K, Tsurumi T, Yamaguchi K.
    • Journal Title

      Immunol Lett. 95(2)

      Pages: 199-205

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expansion of human CMV-specific cytotoxic T lymphocytes to a clinical scale : a simple culture system using tetrameric HLA-peptide complexes.2004

    • Author(s)
      Watanabe N, Kamachi Y, Koyama N, Hama A, Liang J, Nakamura Y, Yamamoto T, Isomura M, Kudo K, Kuzushima K, Kojima S.
    • Journal Title

      Cytotherapy. 6(5)

      Pages: 514-522

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expansion of human CMV-specific cytotoxic T lymphocytes to a clinical scale : a simple culture system using tetrameric HLA-peptide complexes.2004

    • Author(s)
      Watanabe N.
    • Journal Title

      Cytotherapy 6(5)

      Pages: 514-522

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A^*2402-restricted cytotoxic T-lymphocyte responses.2004

    • Author(s)
      Tajima K.
    • Journal Title

      Tissue Antigens 64(6)

      Pages: 650-659

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interferon-γ differentially regulates susceptibility of lung cancer cells to telomerase-specific cytotoxic T lymphocytes.2004

    • Author(s)
      Tajima K.
    • Journal Title

      Int.J.Cancer 110(3)

      Pages: 403-412

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Quantitative analysis of Epstein-Barr virus (EBV)-specific CD8+ T cells in patients with chronic active EBV infection.2004

    • Author(s)
      Sugaya N.
    • Journal Title

      J.Infect.Dis. 190(5)

      Pages: 985-988

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Immunity against mouse thymus-leukemia antigen protects against development of lymphomas induced by a chemical carcinogen, N-butyl-N-nitrosourea.2004

    • Author(s)
      Tsujimura K.
    • Journal Title

      Cancer Sci. 95(11)

      Pages: 914-919

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Tetramer-assisted identification and characterization of epitopes recognized by HLA A*2402-restricted Epstein-Barr virus-specific CD8^+ T cells.2003

    • Author(s)
      Kuzushima K.
    • Journal Title

      Blood 101

      Pages: 1460-1468

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Flow cytometric analysis of cytomegalovirus-specific cell-mediated immunity in the congenital infection.2003

    • Author(s)
      Hayashi N.
    • Journal Title

      J.Med.Virol. 71

      Pages: 251-258

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tetramer-assisted identification and characterization of epitopes recognized by HLA A^*2402-restricted Epstein-Barr virus-specific CD8^+ T cells.2003

    • Author(s)
      Kuzushima, K., Hayashi, N., Kudoh, A., Akatsuka, Y., Tsujimura, K., Morishima, Y., Tsurumi, T.
    • Journal Title

      Blood 101(4)

      Pages: 1460-1468

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Flow cytometric analysis of cytomegalovirus-specific cell-mediated immunity in the congenital infection.2003

    • Author(s)
      Hayashi, N., Kimura, H., Morishima, T., Tanaka, N., Tsurumi, T., Kuzushima, K.
    • Journal Title

      J.Med.Virol. 71(2)

      Pages: 251-258

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Kuzushima K.: "Tetramer-assisted identification and characterization of epitopes recognized by HLA-A2402-restricted EBV-specific CD8^+ T cells"Blood. 101・4. 1460-1468 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kudoh A.: "Reactivation of lytic replication from B cells latently infected with EBV Occurs with high S-phase cyclin-dependent kinase activity while inhibiting cellular DNA"J.Virol.. 77・2. 851-861 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hayashi N.: "Flow cytometric analysis of cytomegalovirus-specific cell-mediated immunity in the congenital infection"J.Med.Virol.. 71・2. 251-258 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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