Effects of HLA alleles on antiviral activity of T cells

• Project/Area Number: 19590479
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Kumamoto University
• Principal Investigator: UENO Takamasa Kumamoto University, エイズ学研究センター, 准教授 (10322314)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: ワクチン / HLA / 細胞傷害性T細胞 / HIV / HLAクラスI / 細胞障害性T細胞 / Nef / 安定性 / 淘汰圧

Research Abstract

HIVなどヒトに慢性疾患を引き起こすウイルス感染症では、病態の進行がHLAアリルのハプロタイプと相関するが、その要因は明らかになっていない。本研究では、HLAアリル多型性がT細胞の抗ウイルス機能に与える役割と、ウイルス因子が獲得免疫応答に及ぼす影響を解析した。その結果、(1)HIVに対するCTL免疫監視システムは、HIV-1病原性因子であるNefの機能に著しい影響を与えること、(2)抗原ペプチド・MHC複合体の安定性が、TCRによる抗原認識を通じて、HIV特異的CTLの抗ウイルス活性に大きく影響すること、の二点を明らかにした。

Research Products

• [Journal Article] Impact of intrinsic cooperative thermodynamics of peptide-MHC complexes on antiviral acivity of HIV-specific CTL (2009)
  • Author(s): Chihiro Motozono, Saeko Yanaka, Kouhei Tsumoto, Masafumi Takiguchi, Takamasa Ueno
  • Journal Title: Journal of Immunology 182 Pages: 5528-5536
  • Peer Reviewed
• [Journal Article] Impact of intrinsic cooperative thermodynamics of peptide-MHC complexes on antiviral activity of HIV-specific CTLs (2009)
  • Author(s): Chihiro Motozono
  • Journal Title: Journal of Immunology in press
  • Peer Reviewed
• [Journal Article] CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef (2008)
  • Author(s): Takamasa Ueno, Chihiro Motozono, Sachi Dohki, Philip Mwimanzi, Susanne Rauch, Oliver T. Fackler, Shinichi, Oka, Masafumi Takiguchi
  • Journal Title: Journal of Immunology 180 Pages: 1107-1116
  • Peer Reviewed
• [Journal Article] Determination of a major histocompatibility complex class I restricting simian immunodeficiency virus Gag241-249 epitope (2008)
  • Author(s): Tetsuo Tsukamoto, Sachi Dohki, Takamasa Ueno, Miki Kawada, Akiko Takeda, Michio Yasunami, Taeko Naruse, Akinori Kimura, Masafumi Takiguchi, and Tetsuro Matano
  • Journal Title: AIDS 22 Pages: 993-994
  • Peer Reviewed
• [Journal Article] CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef (2008)
  • Author(s): Takamasa Ueno
  • Journal Title: Journal of Immunology 180 Pages: 1107-1116
  • Peer Reviewed
• [Journal Article] Determination of a major histocompatibility complex class I restricting simian immunodeficiency virus Gag241-249 epitope (2008)
  • Author(s): T. Tsukamoto
  • Journal Title: AIDS 22 Pages: 993-994
  • Peer Reviewed
• [Journal Article] Cytotoxic T lymphocyte-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef (2008)
  • Author(s): Takamasa Ueno
  • Journal Title: Journal of Immunology 180 Pages: 1107-1116
  • Peer Reviewed
• [Journal Article] Altering effects of antigenic variations in HIV-1 on antiviral effectiveness of HIV-specific CTLs (2007)
  • Author(s): Takamasa Ueno, Yuka Idegami, Chihiro Motozono, Shinichi, Oka, Masafumi Takiguchi
  • Journal Title: Journal of Immunology 178 Pages: 5513-5523
  • Peer Reviewed
• [Journal Article] Altering effects of antigenic variations in HIV-1 on antiviral effectiveness of HIV-specific CTLs (2007)
  • Author(s): Takamasa Ueno
  • Journal Title: Journal of Immunology 178 Pages: 5513-5523
  • Peer Reviewed
• [Presentation] Antiviral activity of HIV-specific cytotoxic T lymphocytes is influenced by intrinsic cooperative thermodynamics of peptide-MHC complexes (2009)
  • Author(s): C. Motozono, S. Yanaka, K. Tsumoto, M. Takiguchi, Takamasa Ueno
  • Organizer: Keystone Syposium -HIV immunobiology : From Infection to Immune Control, Keystone Resort, Keystone
  • Place of Presentation: Colorado, USA
• [Presentation] The effects of CTL-escape conferring mutations on Nef's pathogenic functions in primary macrophages (2009)
  • Author(s): Philip Mwimanzi, M. Fujiwara, M. Takiguchi, Takamasa Ueno
  • Organizer: Keystone Symposium -HIV immunobiology : From Infection to Immune Control, Keystone Resort, Keystone
  • Place of Presentation: Colorado, USA
• [Presentation] The effect of TCR-peptide-MHC interactions on antiviral activity and cross-reactive capacity of HIV-specific CTLs (2008)
  • Author(s): Chihiro Motozono, Masafumi Takiguchi, and Takamasa Ueno
  • Organizer: Keystone Symposia -HIV Pathogenesis-
  • Place of Presentation: Banff, Canada
• [Presentation] CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef (2008)
  • Author(s): Takamasa Ueno, Chihiro Motozono, Sachi Douki, Susanne Rauch, Philip Mwimanzi, Oliver T. Fackler, Shinichi Oka, Masafumi Takiguchi
  • Organizer: XVII International AIDS Conference
  • Place of Presentation: Mexico City
• [Presentation] The decay of peptide-MHC complex influences antiviral activity of HIV-specific CTLs (2008)
  • Author(s): Chihiro Motozono, Masafumi Takiguchi, Takamasa Ueno
  • Organizer: 9th AIDS Seminar in KUMAMOTO
  • Place of Presentation: Kumamoto, Japan
• [Presentation] The effects of CTL-escape conferring mutations on Nef's pathogenic functions in primary macrophages (2008)
  • Author(s): Philip Mwimanzi, Mamoru Fujiwara, Masafumi Takiguchi, Takamasa Ueno
  • Organizer: 9th AIDS Seminar in KUMAMOTO
  • Place of Presentation: Kumamoto, Japan
• [Presentation] The balance of power : Nef and CTL (2008)
  • Author(s): Takamasa Ueno
  • Organizer: 9th AIDS Seminar in KUMAMOTO
  • Place of Presentation: Kumamoto, Japan
• [Presentation] HIV特異的T細胞の抗原特異性と抗原変異に対する交差反応性、一般口演「レンチウイルス、HIV(7)」 (2008)
  • Author(s): 本園千尋、滝口雅文、上野貴将
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
• [Presentation] 抗原ペプチド複合体の内在的安定性はCTLの抗ウイルス活性に影響する、一般口演「O-37)免疫」 (2008)
  • Author(s): 本園千尋、滝口雅文、上野貴将
  • Organizer: 第22回日本エイズ学会学術集会・総会
  • Place of Presentation: 大阪国際交流センター
• [Presentation] ヒト免疫監視システムとHIVの適応馴化シンポジウム「ヒトはなぜエイズになるのか」 (2008)
  • Author(s): 上野貴将
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪国際交流センター
• [Presentation] 抗原ペプチド・MHC複合体の安定性はT細胞の抗ウイルス機能に影響する、ワークショップ「ウイルス感染-2」 (2008)
  • Author(s): 本園千尋、滝口雅文、上野貴将
  • Organizer: 第38回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] The effects of CTL-escape conferring mutations on Nef's pathogenic functions in primary macrophages、一般口演「O-35)アクセサリー」 (2008)
  • Author(s): Mwimanzi Philip、藤原守、滝口雅文、上野貴将
  • Organizer: 第22回日本エイズ学会学術集会・総会
  • Place of Presentation: 大阪国際交流センター
• [Presentation] 抗原ペプチド・ MHC複合体の安定性はT細胞の抗ウイルス機能に影響する (2008)
  • Author(s): 本園千尋
  • Organizer: 第38回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] ヒト免疫監視システムとHIVの適応馴化 (2008)
  • Author(s): 上野貴将
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪国際交流センター
• [Presentation] The effects of CTL-escape conferring mutations on Nef's pathogenic functions in primary macrophages (2008)
  • Author(s): Philip Mwimanzi
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪国際交流センター
• [Presentation] The effect of TCR-peptide-MHC interactions on antiviral activity and cross-reactive capacity of HIV-specific CTLs (2008)
  • Author(s): Chihiro Motozono
  • Organizer: Keystone Symposia-HIV Pathogenesis
  • Place of Presentation: Banff,Canada
• [Presentation] CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef (2007)
  • Author(s): 上野貴将、本園千尋、道木佐知、Philip Mwimanzi、岡慎一、滝口雅文
  • Organizer: ワークショップ第37回日本免疫学会総会・学術集会
  • Place of Presentation: 高輪プリンスホテル
  • Year and Date: 2007-11-20
• [Presentation] CTL-mediated selective pressure modulates pathogenic functions of HIV-1 Nef (2007)
  • Author(s): Takamasa Ueno, Chihiro Motozono, Sachi Douki, Shinichi Oka, Masafumi Takiguchi
  • Organizer: Keystone Symposia-Molecular and Cellular Determinants of HIV Pathogenesis-
  • Place of Presentation: Whistler, Canada
• [Presentation] CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef (2007)
  • Author(s): Takamasa Ueno, Chihiro Motozono, Sachi Douki, Susanne Rauch, Philip Mwimanzi, Oliver T. Fackler, Shinichi Oka, Masafumi Takiguchi
  • Organizer: AIDS Vaccine 07
  • Place of Presentation: Seattle, USA
• [Presentation] The impact of CTL-mediated selective forces on pathogenic functions of HIV-1 Nef (2007)
  • Author(s): Takamasa Ueno
  • Organizer: Center for AIDS Research, Kumamoto University, 10th Anniversary Symposium
  • Place of Presentation: Kumamoto, Japan
• [Presentation] The capacity of antigenic peptides that dictates antiviral activity of Cytotoxic T Lymphocytes (2007)
  • Author(s): Chihiro Motozono, Masafumi Takiguchi, Takamasa Ueno
  • Organizer: 8th AIDS Seminar in KUMAMOTO
  • Place of Presentation: Kumamoto, Japan
• [Presentation] Ability of HIV-1-specific CTL to suppress HIV-1 replication and selection of escape mutants in chronically HIV-1-infected individuals (2007)
  • Author(s): Koizumi, H., Iwatani, T., Hachiya, A., Kawashima, Y., Ueno, T., Oka, S., and Takiguchi, M.
  • Organizer: 8th AIDS Seminar in KUMAMOTO
  • Place of Presentation: Kumamoto, Japan
• [Presentation] CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef (2007)
  • Author(s): Takamasa Ueno, Chihiro Motozono, Sachi Douki, Susanne Rauch, Philip Mwimanzi, Oliver T. Fackler, Shinichi Oka, Masafumi Takiguchi
  • Organizer: 8th AIDS Seminar in KUMAMOTO
  • Place of Presentation: Kumamoto, Japan
• [Presentation] HIV Nefの病原性機能維持と宿主免疫淘汰圧ワークショップ (2007)
  • Author(s): 上野貴将、本園千尋、道木佐知、岡慎一、滝口雅文
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター
• [Presentation] CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef (2007)
  • Author(s): T.Ueno
  • Organizer: AIDS Vaccine Conference
  • Place of Presentation: Seattle,WA.U.S.A.
• [Presentation] HIV Nefの病原性機能維持と宿主免疫淘汰圧 (2007)
  • Author(s): 上野 貴将
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター
• [Book] HIV感染症-宿主側の防衛因子の役割-「HIVコントロールにおけるCTLの役割」血液フロンティア (2008)
  • Author(s): 上野貴将、本園千尋
  • Publisher: 医薬ジャーナル社
• [Book] アイソトープのヒト免疫研究への活用細胞工学別冊実験プロトコールシリーズ (2007)
  • Author(s): 上野貴将
  • Publisher: 秀潤社
• [Patent(Industrial Property Rights)] T細胞受容体を模倣する抗体断片及びその製造方法 (2008)
  • Inventor(s): 熊谷泉、梅津光央、渡邊秀樹、上野貴将、本園千尋
  • Industrial Property Rights Holder: 熊谷泉、梅津光央、渡邊秀樹、上野貴将、本園千尋
  • Industrial Property Number: 2008-135007
  • Filing Date: 2008-05-23
• [Patent(Industrial Property Rights)] 特許権 (2008)
  • Inventor(s): 熊谷泉
  • Industrial Property Rights Holder: 同左
  • Industrial Property Number: 2008-135007
  • Filing Date: 2008-05-23