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Structural analysis of protective and non-protective T-cell epitopes encoded with in the retroviral gag gene product

Research Project

Project/Area Number 13670305
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MIYAZAWA Masaaki  Kinki Univ., School of Medicine, Professor, 医学部, 教授 (60167757)

Co-Investigator(Kenkyū-buntansha) KAWAHARA Sachiyo (TSUJI SACHIYO)  Kinki Univ., School of Medicine, Research Associate, 医学部, 助手 (60297629)
TABATA Nobutada  Kinki Univ., School of Medicine, Research Associate, 医学部, 講師 (40298948)
MATSUMURA Haruo  Kinki Univ., School of Medicine, Instructor, 医学部, 講師 (10229536)
ABE Hiroyuki  Kinki Univ., School of Medicine, Instructor, 医学部, 助手 (80309335)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Keywordsretroviruses / immunity / vaccine / cytokines / gag gene / MA protein / myristylation / epitope / 抗原エピトープ / 組換えウイルス / Tリンパ球 / 合成ペプチド / MHC
Research Abstract

1) One of the mouse retroviral gag gene products, the N-terminal MA protein, contains multiple T-lymphocyte epitopes recognized by CD4-positive helper cells. One of these T-helper cell epitopes was mapped within amino acid residues 62 and 76, and another epitope was localized between residues 119 and 138 in the MA protein.
2) CD4-positive T cells specifically reacting to the 62-76 epitope produced a large amount of IL-4, while T cells reactive to the epitope within 119-138 did not.
3) To identify the antigenic structures that are required for protection against retroviral infection, various truncated forms of MA were expressed in a newly modified vaccinia virus vector, and mice were immunized with the resultant recombinant vaccinia viruses. All the truncated forms of MA lost the ability to protect mice, while the entire MA was effective. To elucidate if the truncation in the N-terminal portion affected the effectiveness of the whole MA due to the lack of the N-terminal residue required for protein myristylation, Gly at residue 2 was replaced with Ala in a mutant MA. This mutant MA localized in the cell nuclei, instead of cell membrane where myristylated proteins normally accumulate, and at the same time the vaccinia virus expressing this mutant MA lost its ability to protect mice against retroviral infection.
4) Thus, myristylation of MA is necessary for its proper immunogenicity, and when myristylated, the Th2 epitope is not necessary, but an epitope in the C-terminal portion is required for protective efficacy of MA.

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Iwanami, N.: "Role of natural killer cells in resistance against Friend retrovirus-induced leukemia"J.Virol.. 75. 3152-3163 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuji, S.: "B cell adaptor containing Src homology 2 domain (BASH) links B cell receptor signaling to the activation of hematopoietic progenitor kinase 1"J.Exp.Med.. 194. 529-539 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuoka, K.: "Changes in the number of gut mucosal T-lymphocytes and macrophages in patients treated by external biliary drainage"Eur.J.Surg.. 167. 684-688 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugita, J.: "Close association of Fas ligand-positive tumor-associated macrophages and apoptotic cancer cells along invasive margins of colorectal carcinoma interactions"Jpn.J.Cancer Res.. 93. 320-328 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 宮澤 正顯: "マウスレトロウイルス感染と発症:宿主遺伝子による制御機構"ウイルス. 52. 69-76 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 宮澤 正顯: "からだを守る"昭和堂. 168 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwanami, N., A. Niwa, Y. Yasutomi, N. Tabata, and M. Miyazawa: "Role of natural killer cells in resistance against Friend retrovirus-induced leukemia."J. Virol.. 75. 3152-3163 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuji. S. M. Okamoto, K. Yamada, N. Okamoto, R. Goitsuka, R. Arnold, F. Kiefer, and D. Kitamura: "B cell adaptor containing Src homology 2 domain (BASH) links B cell receptor signaling to the activation of hematopoietic progenitor kinase 1"J. Exp. Med. 194. 529-539 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuoka, K., T. Ajiki, M. Miyazawa. Y. Takayama, H. Onoyama, and Y. Kuroda.: "Changes in the number of gut mucosal T-lymphocytes and macrophages in patients treated by external biliary drainage."Eur. J. Surg.. 167. 684-688 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugita, J., H. Ohtani, T. Mizoi, K. Saito, K. Shiiba, I. Sasaki, S. Matsuno, H. Yagita, M. Miyazawa, and H. Nagura: "Close assocoation between Fas ligand (FasL; CD95L)-positive rumor-associated macrophages and apoptotic cancer cells along invasive margins of colorectal carcinoma: a proposal on tumor-host interactions."Jpn. J. Cancer Res.. 93. 320-328 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugita, J.: "Close association between Fas ligand-positive tumor-associated macrophages and apoptotic cancer cells invasive margins of colorectal carcinoma"Jpn. J. Cancer Res.. 93. 320-328 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 宮澤 正顯: "免疫系の最新基本概念"看護. 54. 38-42 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 宮澤 正顯: "内在性レトロウイルスと自己免疫疾病自然発生モデル動物"リウマチ科. 27. 218-226 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 宮澤 正顯: "マウスレトロウイルス感染と発症:宿主遺伝子による制御機構"ウイルス. 52. 69-76 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwanami, N. et al.: "Role of natural killer cells in resistance against Friend retrovirus-induced leukemia"Journal of Virology. 75・7. 3152-3163 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuji, S. et al.: "B cell adaptor containing Src homology 2 domain (BASH) links B cell receptor signaling to the activation of hematopoietic PK1"Journal of Experimental Medicine. 194・4. 529-539 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukuoka, K. et al.: "Changes in the number of gut mucosal T-lymphocytes and macrophages in patients treated by external biliary drainage"European Journal of Surgery. 167. 684-688 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 宮澤 正顕: "自己抗原の分子相同性"組織培養工学. 27・5. 175-179 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 山岸秀夫, 宮澤正顕: "からだを守る"昭和堂(京都市). 168 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2022-01-20  

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