2004 Fiscal Year Final Research Report Summary
Research of T cell immunity to Epstein-Barr virus latent membrane protein 1.
| Project/Area Number |
15590429
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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 | Aichi Cancer Center |
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Principal Investigator |
KUZUSHIMA Kiyotaka Aichi Cancer Center, Division of Immunology, Chief, 腫瘍免疫学部, 部長 (30311442)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Epstein-Barr virus / cytotoxic T lymphocyte / proteasome / HLA / short hairpin RNA |
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| 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.
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Research Products
(21 results)
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[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.
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Journal Title
J.Infect.Dis. 190(5)
Pages: 985-988
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Int.J.Cancer 110(3)
Pages: 403-412
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
2004.Blood 103
Pages: 630-638
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Int.J.Hematol. 80(5)
Pages: 441-448
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Cytotherapy. 6(5)
Pages: 514-522
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Blood 101(4)
Pages: 1460-1468
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
J.Med.Virol. 71(2)
Pages: 251-258
Description
「研究成果報告書概要(欧文)」より
