2006 Fiscal Year Final Research Report Summary
Research of Epstein-Barr virus-specific T cell immunity targeting the virus-positive cancer
| Project/Area Number |
17590428
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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 Research Institute |
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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) |
2005 – 2006
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| Keywords | Epstein-Barr virus / CD4^+ T cells / EBNA1 / HLA / lymphoma |
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| Research Abstract |
Epstein-Barr virus (EBV) nuclear antigen (EBNA) 1 is expressed in every EBV-infected cell, regardless of the state of EBV infection. Although EBNA1 is thought to be a promising antigen (Ag) for immunotherapy of all EBV-associated malignancies, it is less clear whether EBNA1-specific CD4^+ T cells can act as direct effectors. Here, we investigated the ability of CD4^+ T cell clones induced with overlapping peptides covering the C-terminal region of EBNA1, and identified minimal epitopes and their restricted MHC class II molecules. Of these, a novel epitope was found to be is presented by DRB1^*0401, 0403, and 0406. Five CD4^+ T cell clones recognized endogenously processed and presented antigens on EBV-transformed lymphoblastoid cell lines and one example proved capable of killing EBV-carrying NK and T cell lines derived from patients with chronic active EBV infection. Identification of minimal epitopes facilitates design of peptide-based vaccines and our data suggest that EBNA1-specific CD4^+ T cells may play roles as direct effectors for immunotherapy targeting EBV-carrying NK and T cell malignancies.
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[Journal Article] Identification of an HLA-A24-restricted cytotoxic T lymphocyte epitope from human papillomavirus type-16 E6 : The combined effects of bortezomib and interferon-gamma on the presentation of a cryptic epitope.2007
Author(s)
Morishima S, Akatsuka Y, Nawa A, Kondo E, Kiyono T, Torikai H, Nakanishi T, Ito Y, Tsujimura K, Iwata K, Ito K, Kodera Y, Morishima Y, Kuzushima K, Takahashi T
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Journal Title
Int J Cancer. 120
Pages: 594-604
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Epstein-Barr virus (EBV) latent membrane protein 1-specific cytotoxic T lymphocytes targeting natural killer cell malignancies carrying EBV.2006
Author(s)
Demachi-Okamura, A., Ito, Y., Akatsuka, Y., Tsujimura, K., Morishima, Y., Takahashi, T., Kuzushima, K.
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Journal Title
Eur.J.Immunol 36(3)
Pages: 593-602
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Three Immunoproteasome-Associated Subunits Cooperatively Generate a CTL Epitope of the EBV LMP2A by Overcoming Specific Structures Resistant to Epitope Liberation.2006
Author(s)
Ito, Y., Kondo, E., Demachi-Okamura, A., Akatsuka, Y., Tsujimura, K., Tanimoto, M., Morishima, Y., Takahashi, T., Kuzushima, K.
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Journal Title
J Virol 80(2)
Pages: 883-890
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The human cathepsin H gene encodes two novel minor histocompatibility antigen epitopes restricted by HLA-A^*3101 and-A^*3303.2006
Author(s)
Torikai H, Akatsuka Y, Miyazaki M, Tsujimura A, Yatabe Y, Kawase T, Nakao Y, Tsujimura K, Motoyoshi K, Morishima Y, Kodera Y, Kuzushima K, Takahashi T
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Journal Title
Br J Haematol 134(4)
Pages: 406-416
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Generation of tumor-specific, HLA class I-restricted human Th1 and Tc1 cells by cell engineering with tumor peptide-specific T-cell receptor genes.2005
Author(s)
Tsuji, T., Yasukawa, M., Matsuzaki, J., Ohkuri, T., Chamoto, K., Wakita, D., Azuma, T., Niiya, H., Miyoshi, H., Kuzushima.K., Oka, Y., Sugiyama, H., Ikeda, H., Nishimura, T.
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Journal Title
Blood. 106(2)
Pages: 470-476
Description
「研究成果報告書概要(欧文)」より
