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Prevention of viral infection by helper T cell-epitope vaccine and analysis of its basic mechanism

Research Project

Project/Area Number 08457095
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionMie University

Principal Investigator

KURIBAYASHI Kagemasa  Mie University Faculty of Medicine Department of Bioregulation Professor, 医学部, 教授 (10064578)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1996: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordsvirus / vaccine / helper T cell / peptide antigen / CTL / Fas / Perforin / ウィルス感染 / T細胞エピトープ / Th細胞 / 細胞傷害 / Fas-FasL / ウイルス感染防御
Research Abstract

Effector T cells are generated in syngeneic or semisyngeneic mice after rejection of Friend virus-induced tumor FBL-3. Using FBL-3-specific helper T cell (Th) and cytotoxic T lymphocyte (CTL) clones, we have identified two species of Th epitope (one is I-A^b-binding, the other I-E^b binding) and one CTL epitope which bind to H2D^b. Immunization with the I-E^b binding synthetic peptide effectively prevented susceptible mice from the occurrence of erythroleukemia by Friend virus infection. Effects of I-A^b-binding syhthetic peptide on the prevention was much weaker than that by the I-E^b binding synthetic peptide.
Unexpectedly, most of the Th clones which were established on the basis of their proliferative activities showed peptide-specific cytotoxicity in the context of MHC class II.Alanine substitution of MHC or T cell receptor (TCR) contacting residues in the Th peptides abolished the proliferation of all the Th clones examined. However, the cytotoxic activities of the same Th colnes were little affected by the corresponding mutated peptides. This suggested that recognition of MHC-peptide complexes by Th cells for cytotoxicity is more flexible than that for the stimulation of proliferation. Furthermore, cytolytic machinery used in the Th clones were dependent upon one of the followings : Fas-FasL interaction, perforin-mediated granular exocytosis, and both of the two machineries. These findings might provide a new insight for developing an effective vaccine for viral infection and its prevention.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] H.Uenishi et al.: "Overlapping epitopes of Friend murine leukemia virus-gag-encoded leader sequences recognized by single cytotoxic T-lymyphocyte clones" Immunclogy Letter. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Uenishi et al.: "Induction of cross-reactivity in an endogenous viral peptide non-reactive to FBL-3 tumor-specific helper T cell clone" Microbiology and Immunology. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Yasutomi: "Elexible recognition of antigenic peptides with mutated swquence by CD4^+ CTL:Comparison with the requirement for proliferation and analysis of their cytolytic mechanisons" (Submitted to publication).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hirohide Uenishi, Norimasa Iwanami, Kagemasa Kuribayashi, Hirokazu Tamura, Nobutaka Fujii, Takako Nakatani, Toshisuke Kawasaki, and Hideo Yamagishi: "Overlapping epitopes of Friend murine leukemia virus gag-encoded leader sequence recognized by single cytotoxic T-lymphocyte clones." Immunol.Lett.(In press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hirohide Uenishi, Norimasa Iwanami, Hideo Yamagishi, Takako Nakatani, Toshisuke Kawasaki, Hirokazu Tamamura, Nobutaka Fujii and Kagemasa Kuribayashi: "Induction of cross-reactivity in an endogenous viral peptide non-reactive to FBL-3 tumor-specific helper T cell clones." Microbiol.Immunol.(In press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yasuhiro Yasutomi, Hirohide Uenishi, Hideo Yamagishi, and Kagemasa Kuribayashi: "Flexible recognition of antigenic peptides with mutated sequence by CD4^+ CTL : Comparison with the requirement for proliferation and analysis of their cytolytic mechanisms" (Submitted to publication).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Uenishi,H.et al.: "Overlapping epitopes of Friend murine leukemia virus gag-encoded leader sequence recognized by single cytotoxic T lymptrocyte clones" Immunol.Lett.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Uenishi H., et al.: "Induction of cross-reactiuity in endogenous viral peptide non-reactive to FBL-3 tumor-specibic helper T cell clones" Microbiol.Immunol.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikeda,H., et al: "Mutated mitogen-activated protein kinase:A tumur rezection antigen of mouse sarcoma" Proc.Natl.Acad.Sci.USA. 94. 6375-6379 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Schmitt,M., et al.: "Involvement of T-cell subsets and natural killer cells(NK)in the growth suppressin of murine bibrosarcoma cells transfected with interlenkin(IL)-12 genes" Int.J.Cancer. 72. 505-511 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Higo,k., et al.: "Susceptibility of nude mice carrying the FV-4 gene to Friend murine leukemia virus infection" J.Virol.71. 750-754 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kubo,Y., et al.: "Possible origin of murine AIDS(MAIDS)virus:conversion of an endogenous retro-viral qp12gag sequence to a MAIDS-inducing sequence by frameshift mutation" J.Virol.70. 6405-6409 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kyoko Higo: "Suoceptibility of nude mice carrying the FV-4 gene to Friend murine leukemia virus infecte" Journal of Virology. Vol71・1. 750-754 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshinao Kubo: "Possible origin of murine AIDS(MAIDS)virus:Conversion of an endogenous retroviral P12^<gag> sequence to a MAIDS-inducing sequence by franceshigt mutations." Journal of Virology. Vol.70・9. 6405-6409 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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