Analysis of HIV-specific cellular immune response and antigen presentation in HIV infection

• Project/Area Number: 19390130
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: The University of Tokyo
• Principal Investigator: IWAMOTO Aikichi The University of Tokyo, 医科学研究所, 教授 (10133076)
• Co-Investigator(Kenkyū-buntansha): TACHIKAWA Ai 東京大学, 医科学研究所, 助教 (10396880)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2008: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2007: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
• Keywords: HIV / HLA / 細胞傷害性T 細胞 (CTL) / 抗原認識 / エピトープ / 細胞傷害性T細胞(CTL) / T細胞受容体(TCR) / TCR レパートリー / HIV病態進行

Research Abstract

HIV は抗原性を変化させることで細胞傷害性T リンパ球(CTL)による免疫監視機構から逃れている。本研究ではHIV 抗原の質的変化に対する細胞性免疫応答の解析を行った。HIV 感染者体内には「変化したHIV 抗原」を認識するCTL は存在するが、その多様性は低く、疲弊した状態に陥っていることが明らかとなった。また、HIV 抗原の変化は集団レベルにおけるHIV の病原性にも影響を与える可能性が示唆された。

Research Products

• [Journal Article] Highly restricted T-cell receptor repertoire in the CD8+ T-cell response against an HIV-1 epitope with a stereotypic amino acid substitution (2009)
  • Author(s): Miyazaki, E., Kawana-Tachikawa, A., Tomizawa, M., Nunoya J-I., Odawara T., Fujii, T., Shi, Y., Gao G.F., Iwamoto, A.
  • Journal Title: AIDS 23 Pages: 651-660
• [Journal Article] Rehsusmacaque : a tight homodimeric CD8alpha/alpha (2009)
  • Author(s): Zong, L., Chen, Y., Peng, H., Gao, F., Iwamoto, A., Gao, GF.
  • Journal Title: Proteins : Structure, Function and Bioinformatics 75 Pages: 241-244
• [Journal Article] Activation of HIV-1 Gag-specific CD8+ T cells by yeast-derived VLP-pulsed dendritic cells is influenced by the level of mannose on the VLP antigen (2009)
  • Author(s): Mizukoshi, F., Yamamoto, T., Mitsuki Y.Y., Terahara, K., Kawana-Tachikawa, A., Kobayashi, K., Iwamoto A., Morikawa, Y., Tsunetsugu-Yokota, Y.
  • Journal Title: Microbes Infection 11 Pages: 191-19
• [Journal Article] Highly restricted T-cell receptor repertoire in the CD8+T-cell response against an HIV-1 epitope with stereotypic amino acid substitution. (2009)
  • Author(s): Miyazaki, E
  • Journal Title: AIDS 23 Pages: 651-660
  • Peer Reviewed
• [Journal Article] Generation of recombinant monoclonal antibodies against an immunodominant HLA-A*2402-restficted HIV-1 CTL epitope. (2009)
  • Author(s): Nuhoya, J.
  • Journal Title: AIDS Research and Human Retroviruses (In press)
  • Peer Reviewed
• [Journal Article] Activation of HIV-1 Gag-specific CD8+T cells by yeast-derived VLP-pulsed dendritic cells is innuenced by the level of mannose on the VLP antigen. (2009)
  • Author(s): Mizukoshi, F.
  • Journal Title: Microbes Infection 11 Pages: 191-197
  • Peer Reviewed
• [Journal Article] Rehsusmacaque: a tight homodimeric CD8alpha/alpha. Proteins. (2009)
  • Author(s): Zong, L.
  • Journal Title: Structure, Function and Bioinformatics 75 Pages: 241-244
  • Peer Reviewed
• [Journal Article] Pneumocystis jiroveci pneumonia in an AIDS patient:Unusual manifestation of multiple nodules with multiloculated cavities. (2009)
  • Author(s): Maeda, T
  • Journal Title: European Journal of Radiology (In press)
  • Peer Reviewed
• [Journal Article] Comparison between Sendai virus and Adenovirus vectors in induction of HIV-1 genes into human dendritic cells (2008)
  • Author(s): Hosoya, N., Miura, T., Kawana-Tachikawa, A., Shioda, T., Odawara, T.,Nakamura, T., Kitamura, Y., Kano, M., Kato, A., Hironaka, T., Hasegawa, M.,Nagai, Y., Iwamoto, A.
  • Journal Title: J. Medical Virology 80 Pages: 373-382
• [Journal Article] Erythromycin derivatives inhibit HIV-1 replication in macrophages through modulation of MAPK activity to induce small isoforms of C/EBPbeta (2008)
  • Author(s): Komuro, I., Sunazuka, T., Akagawa, K.S., Yokota, Y., Iwamoto, A., Omura, S.
  • Journal Title: Proc. Natl. Acad. USA 105 Pages: 12509-12514
• [Journal Article] Erythromycin derivatives inhibit HIV-1 replication in Macrophages through modulation of MAPK activity to induce small isoforms of C/EBPbeta. (2008)
  • Author(s): Komuro, I
  • Journal Title: Proc. Natl Acad.USA. 105 Pages: 12509-12514
  • Peer Reviewed
• [Journal Article] Polymorphisms in CCR5 chemokine receptorgene in Japan. International J (2007)
  • Author(s): Liu, H., Nakayama, E.E., Theodorou, I., Nagai, Y., Likanonsakul, S., Wasi, C., Debre, P. Iwamoto, A., Shioda, T.
  • Journal Title: Immunogenetics 34 Pages: 325-335
• [Journal Article] Wild type and H43Y variant of human TRIM5α show similar anti-human immunodeficiency virus type 1 activity both in vivo and in vitro (2007)
  • Author(s): Nakayama, E.E., Carpentier, W., Costagliola, D., Shioda, T., Iwamoto, A., Debre, P., Yoshimura, K., Autran, B., Matsushita, S., Theodorou, I.
  • Journal Title: International J.Immunogenetics 59 Pages: 511-515
• [Journal Article] A three-base-deletion polymorphism in the upstream non-coding regionof human interleukin 7 (IL-7) gene could enhance levels of IL-7 expression (2007)
  • Author(s): Song, H., Nakayama, E.E., Likanonsakul, S., Wasi, C., Iwamoto, A., Shioda, T.
  • Journal Title: International J. Immunogenetics 34 Pages: 107-113
• [Journal Article] The polymorphisms in DC-SIGNR affect susceptibility to HIV-1infection (2007)
  • Author(s): Wichukchinda, N., Kitamura, Y., Rojanawiwat, A., Nakayama, E.E., Song, H.,Pathipvanich, P., Auwanit, W., Sawanpanyalert, P., Iwamoto, A., Shioda, T., Ariyoshi, K.
  • Journal Title: Research and Human Retroviruses 23 Pages: 686-692
• [Journal Article] Vpr in plasma of HIV-1-positive patients is correlated with the HIV-1 RNA titers (2007)
  • Author(s): Hoshino, S., Sun, B., Konishi, M., Shimura, M., Segawa, T. Hagiwara, Y.,Koyanagi, Y., Iwamoto, A., Mimaya, J., Terunuma, H., Kano, S., Ishizaka, Y.
  • Journal Title: AIDS Research and Human Retroviruses 23 Pages: 391-397
• [Journal Article] Comparison between Sendai virus and Adenovirus vectors in induction of HIV-1 genes into human dendritic cells (2007)
  • Author(s): Hosoya, N
  • Journal Title: Journal of Medical Virology 80 Pages: 373-382
  • Peer Reviewed
• [Journal Article] Vpr in plasma of HIV-1-positive patients is correlated with the HIV-RNA titers (2007)
  • Author(s): Hoshino, S.
  • Journal Title: AIDS Research and Human Retroviruses 23 Pages: 391-397
  • Peer Reviewed
• [Journal Article] Polymorphisms in CCR5 chemokine receptor gene in Japan (2007)
  • Author(s): Liu, H.
  • Journal Title: International Journal of Immunogenetics 34 Pages: 325-335
  • Peer Reviewed
• [Journal Article] The polymorphisms in DC-SIGNR affect susceptibility to HIV-linfection (2007)
  • Author(s): Wichukchinda, N.
  • Journal Title: AIDS Research and Human Retroviruses 23 Pages: 686-692
  • Peer Reviewed
• [Journal Article] A three-base-deletion polymorphism in the upstream non-coding regionof human interleukin'7 (IL-7) gene could enhance levels of IL-7 expression (2007)
  • Author(s): Song, H.
  • Journal Title: International Journal of Immunogenetics 34 Pages: 107-113
  • Peer Reviewed
• [Journal Article] Wild type and H43Y variant of human TRIM5α show similar anti-human immunodeficiency virus type 1 activity both in vivo and in vitro (2007)
  • Author(s): Nakayama, E. E.
  • Journal Title: Immunogenetics 59 Pages: 511-515
  • Peer Reviewed
• [Journal Article] Generation of recombinant monoclonal antibodies against an immunodominant HLA-A*2402-restricted HIV-1 CTL epitope
  • Author(s): Nunoya, J-I., Nakashima, T., Kawana-Tachikawa, A., Kiyotani, K., Ito, Y., Sugimura, K., Iwamoto, A.
  • Journal Title: AIDS Research and Human Retroviruses (In press)
• [Journal Article] Pneumocystis jiroveci pneumonia in an AIDS patient : Unusual manifestation of multiple nodules with multiloculated cavities
  • Author(s): Maeda, T., Oyaizu, N., Endo, T., Odawara, T., Nakamura, T., Iwamoto, A., Fujii, T.
  • Journal Title: European Journalof Radiology (In Press)
• [Presentation] Contribution of Gag-specific CD8+ T cells to HIV control in a population lacking HLA-B57/27 (2009)
  • Author(s): Kawana-Tachikawa, A
  • Organizer: Keystone Symposia : HIV Immunology, Infection to Immune Control
  • Place of Presentation: Keystone
• [Presentation] Contribution of Gag-speclfic CD8+ T cells to HIV control in a population lacking HLA-B57/27. (2009)
  • Author(s): Kawana-Tachikawa, A.
  • Organizer: Keystone Symposia: HIV Immunobiology,Infection to Immune Control
  • Place of Presentation: Keystone(アメリカ合衆国)
• [Presentation] 日本人集団においてHLA多型性が慢性感染期血中HIV-1ウイルス量に与える影響の解析 (2008)
  • Author(s): 古賀道子
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 超多剤耐性患者における新規抗HIV 薬Etravirin 、Darunavir 、Raltegravir, の併用効果 (2008)
  • Author(s): 中村仁美
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
• [Presentation] HAARTを施行した.HIV/HBV重複感染者13 例の解析 (2008)
  • Author(s): 鯉渕智彦
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
• [Presentation] HAART導入時に急性肝障害を生じ、1ヶ月後にHBe抗体陽性となったHBVキャリアの1例 (2008)
  • Author(s): 鯉渕智彦
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 特異な経過を辿った結核による免疫再構築症候群の一例 (2008)
  • Author(s): 菊地正
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 既治療患者おける薬剤耐性(多剤耐性)HIVの現状調査 (2008)
  • Author(s): 宮崎菜穂子
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
• [Presentation] HIV セットポイントを規定する免疫関連因子とHIV特異的細胞生免疫応答の解析 (2008)
  • Author(s): 中山香
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
• [Presentation] "Japan and infectious diseases : A historical view." APRU WorldInstitute Workshop (2008)
  • Author(s): Iwamoto, A
  • Organizer: Strengthening Public Health Systems in the Pacific Rim : TheRole of Research Universities in Responding to Aging & Chronic Diseases, Infectious Disease and Health Security Issues
  • Place of Presentation: Tokyo
• [Presentation] Maintenance of Proliferative PD-1 low Memory CD8+ T cells Specific forEradicated Virus in HIV-1 Patients with High CD4 Count (2008)
  • Author(s): Kawana-Tachikawa, A
  • Organizer: 15th Conference onRetroviruses and Oppertunistic Infections
  • Place of Presentation: Boston
• [Presentation] Japan and infectious diseases:A histourical view. (2008)
  • Author(s): Iwamoto, A.
  • Organizer: APRU WorldInstitute Workshop,"Strengthening Public Health Systems in the Pacific Rim:The Role of Research Universities in Responding to Aging & Chronic Diseases, Infectious Disease and Health Security Issues."
  • Place of Presentation: 東京
• [Presentation] HIV セットポイントを規定する免疫関連因子とHIV特異的細胞生免疫応答の解析. (2008)
  • Author(s): 中山香
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
• [Presentation] 超多剤耐性患者における新規抗HIV薬 Etravirin、Darunavir、Raltegravir,の併用効果 (2008)
  • Author(s): 中村仁美
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
• [Presentation] HAARTを施行した,HIV/HBV重複感染者13例の解析 (2008)
  • Author(s): 狸渕智彦
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 既治療患者おける薬剤耐性(多剤耐性)Hrvの現状調査 (2008)
  • Author(s): 宮崎菜穂子
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Maintenance of Proliferative PD-1 low Memory CD8+ T cells Specific forEradicated Virus in HIV-1 Patients with High CD4 Count (2008)
  • Author(s): Kawana-Tachikawa, A.
  • Organizer: 15th Conference onRetroviruses and Oppertunistic Infections
  • Place of Presentation: Boston (USA)
• [Presentation] 抗原の糖鎖による樹状細胞のcross-presentationの影響 (2007)
  • Author(s): 水越文徳
  • Organizer: 第21回日本エイズ学会学術集会
  • Place of Presentation: 広島
• [Presentation] 当院外来患者へのアンケート調査で見られた服薬の問題点と服薬指導の意義 (2007)
  • Author(s): 宮崎菜穂子
  • Organizer: 第21回日本エイズ学会学術集会
  • Place of Presentation: 広島
• [Presentation] HIV treatment and complications (2007)
  • Author(s): Iwamoto, A
  • Organizer: International Conference on AIDS/HIV. China Association of Chinese Medicine AIDS Branch
  • Place of Presentation: Zhengzhou, Henan,China
• [Presentation] Development of a novel IFNgamma detection system of virusspecific T cellactivation by flowcytometry (2007)
  • Author(s): Yamamo, T
  • Organizer: 第37回日本免疫学会学術集会
  • Place of Presentation: 東京
• [Presentation] Antigen presentation and recognition : A tale of immunogenic HIV-1 CTL epitope in Japanese population with high HLA-A24 positivity (2007)
  • Author(s): Iwamoto, A
  • Organizer: International Symposium on Basic and Applied Immunology
  • Place of Presentation: Beijing, China
• [Presentation] HIVセットポイントを規定する免疫関連因子の探索 (2007)
  • Author(s): 中山香
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] HIV由来抗原ペプチドを提示したMHC class I/ペプチド 複合体と特異的に結合する単クローン抗体の作製 (2007)
  • Author(s): 布矢純一
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] A tale of HIV epidemic among highly HLA-A24-positive Japanese population (2007)
  • Author(s): Iwamoto, A
  • Organizer: The 7th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awajishima
• [Presentation] Monitoring and adherence of antiretroviral therapy. In SkillsBuilding Workshop on clinical management of HIV infection and antiretroviral therapy (2007)
  • Author(s): Iwamoto, A
  • Organizer: The 8th International Congress on AIDS in Asia and the Pacific
  • Place of Presentation: Colombo
• [Presentation] Highly restricted T cell receptor repertoire against an immunodominant HIV-1CTL epitope with a stereotypic amino acid substitution (2007)
  • Author(s): Kawana-Tachikawa, A
  • Organizer: 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Sydney
• [Presentation] Generation of monoclonal antibodies cross-reactive for the wildtype and an escape mutant of an immunodominant CTL epitope (2007)
  • Author(s): Nunoya, J-I
  • Organizer: 4th IAS Conferenceon HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Sydney
• [Presentation] HIV epidemic in highly HLA-A24-positive Japanese population (2007)
  • Author(s): Iwamoto, A
  • Organizer: 2007 International Conference for Bioeconomy (BioEco2007)
  • Place of Presentation: Tianjin
• [Presentation] HAARTを施行したHIV/HBV重複感染者の解析 (2007)
  • Author(s): 鯉渕智彦
  • Organizer: 第81回日本感染症学会学術集会
  • Place of Presentation: 京都
• [Presentation] HIV epidemic in highly HLA-A24-positive Japanese population (2007)
  • Author(s): Iwamoto, A.
  • Organizer: International Conference for Bioeconomy (BioEco2007)
  • Place of Presentation: 天津(中国)
• [Presentation] Antigen presentation and recognition : A tale of immunogenic HIV-1 CTL epitope in Japanese population with high HLA-A24 positivity (2007)
  • Author(s): Iwamoto, A.
  • Organizer: International Symposium on Basic and Applied Immunology
  • Place of Presentation: 北京(中国)
• [Presentation] Monitoring and adherence of antiretroviral therapy (2007)
  • Author(s): Iwamoto, A.
  • Organizer: The 8th International Congress on AIDS in Asia and the Pacific
  • Place of Presentation: Colombo (Sri Lanka)
• [Presentation] A tale of HIV epidemic among highly HLA-A24-positive Japanesepopulation (2007)
  • Author(s): Iwamoto, A.
  • Organizer: The 7th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路島
• [Presentation] HIV treatment and complications (2007)
  • Author(s): Iwamoto, A.
  • Organizer: International Conference on AIDS/HIV. China Association of Chinese Medicine AIDS Branch
  • Place of Presentation: 鄭州(中国)
• [Presentation] Highly restricted T cell receptor repertoire against an immunodominant HIV-1CTL epitope with a stereotypic amino acid substitution (2007)
  • Author(s): Kawana-Tachikawa, A.
  • Organizer: 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Sydney (Australia)
• [Presentation] Generation of monoclonal antibodies cross-reactive for the wildtype and an escape mutant of an immunodominant CTL epitope (2007)
  • Author(s): Nunoya, J.
  • Organizer: 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Sydney (Australia)
• [Presentation] 抗原の糖鎖による樹状細胞の cross-presentation の影響 (2007)
  • Author(s): 水越文徳
  • Organizer: 第21回日本エイズ学会学術集会
  • Place of Presentation: 広島
• [Presentation] HAART中の当院外来患者への服薬に関するアンケート調査報告 (2007)
  • Author(s): 宮崎菜穂子
  • Organizer: 第21回日本エイズ学会学術集会
  • Place of Presentation: 広島
• [Presentation] Development of a novel IFNgamma detection system of virus-specific T cellactivation by flow cytometry (2007)
  • Author(s): Yamamoto, T.
  • Organizer: 第37回日本免疫学会学術集会
  • Place of Presentation: 東京