2002 Fiscal Year Final Research Report Summary
Structural analysis of protective and non-protective T-cell epitopes encoded with in the retroviral gag gene product
| Project/Area Number |
13670305
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Kinki University |
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Principal Investigator |
MIYAZAWA Masaaki Kinki Univ., School of Medicine, Professor, 医学部, 教授 (60167757)
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| 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)
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| Project Period (FY) |
2001 – 2002
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| Keywords | retroviruses / immunity / vaccine / cytokines / gag gene / MA protein / myristylation / epitope |
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| 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.
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[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)
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