2007 Fiscal Year Final Research Report Summary
Identification of T-helper peptide-epitopes against gene product of Epstein-Barr virus and Hunan T-cell leukemia virus type I.
| Project/Area Number |
18590360
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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 |
Experimental pathology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
KOBAYASHI Hiroya Asahikawa Medical College, Dept. Pathol., M.D., Ph.D. Assistant Professor (90280867)
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| Project Period (FY) |
2006 – 2007
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| Keywords | EBV / STEAP / HLA / Peptide / Epitope / Helper T lymphocyte / Tumor / Immunotherapy |
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| Research Abstract |
Epstein-Barr virus (EBV)-encoded latent membrane protein l (LMP1) has oncogenic potential and is expressed in many EBV-associated malignancies. Although LMP1 is regarded as a potential tumor associated antigen (TAA) for immunotherapy and several LMP1-specific MHC class I-restricted CTL epitopes have been reported, little is known regarding MHC class II-restricted CD4 helper T lymphocytes (HTL) epitopes for LMP1. The goal of the present studies was to determine whether MHC class II restricted CD4 T cell responses could be induced against the LMP1 antigen and to evaluate the anti-tumor effect of these responses. We have combined the use of a predictive MHC class II binding peptide algorithm with in vitro vaccination of CD4 T cells using candidate peptides to identify naturally processed epitopes derived from LMP1 that elicit immune responses against EBV-expressing tumor cells. Peptide LMP1_<159-175> was effective in inducing HTL responses that were restricted by HLA-DR9, DR53 or DR15, indicating that this peptide behaves as a promiscuous T cell epitope. Moreover, LMP1_<159-175>-reactive HTL clones directly recognized EBV-lymphoblastoid B cells, EBV-infected NK/T lymphoma cells and naturally processed antigen in the form of LMP1+ tumor-cell lysates presented by autologous dendritic cells. Since the newly identified epitope LMP1_<159-175> overlaps with an HLA-A2-restricted CTL epitope (LMP1_<159-175>), this peptide might have ability of inducing simultaneous CTL and HTL responses against LMP1. Overall, our data should be relevant for the design and optimization of T-cell epitope based immunotherapy against various EBV associated malignancies including NK/T cell lymphomas.
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[Journal Article] Induction of EBV-latent membrane protein 1-specific MHC class II-restricted T-cell responses against natural killer lymphoma cells.2008
Author(s)
Kobayashi, H., Nagato, T., Takahara, M., Sato, K., Kimura, S., Aoki, N., Azumi, M., Tateno, M., Harabuchi, Y. and Celis, E.
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Journal Title
Cancer Res. 68
Pages: 901-908
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Recognition of prostate and melanoma tumor cells by six-transmembrane epithelial antigen of prostate-specific helper T lymphocytes in a human leukocyte antigen class II-restricted manner.2007
Author(s)
Kobayashi H, Nagato T, Sato K, Aoki N, Kimura S, Murakami M, Iizuka H, Azumi M, Kakizaki H, Tateno M, Celis E.
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Journal Title
Cancer Res. 67
Pages: 5498-5504
Description
「研究成果報告書概要(欧文)」より
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