Positive and negative regulation of T-cell activation by costimulatory molecules through TCR microclusters

• Project/Area Number: 19590504
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: YOKOSUKA Tadashi The Institute of Physical and Chemical Research, 免疫シグナル研究グループ, 上級研究員 (10359599)
• 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: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 免疫学 / シグナル伝達 / 免疫シナプス / Tリンパ球 / T細胞活性化 / シグナルソーム / プレイナーメンブラン / マイクロクラスター / SMAC

Research Abstract

T細胞の正の副刺激受容体であるCD28が、T細胞受容体(TCR)と共にT細胞活性化の最小単位であるTCRマイクロクラスターを形成すること、CD28下流のシグナル伝達分子としてプロテインキナーゼCθ(PKCθ)を特異的にリクルートすること、また、これらマイクロクラスター形成によってT細胞の増殖やサイトカイン産生が劇的に増強することを明らかにした。この結果から、T細胞の活性化は、TCRと副刺激受容体からなるシグナルソームが時間的空間的に形成され、制御されていることが示唆される。

Research Products

• [Journal Article] Dynamic regulation of T-cell costimulation through TCR?CD28 microclusters (2009)
  • Author(s): Yokosuka T. and Saito T.
  • Journal Title: Immunol. Rev. 229 Pages: 27-40
• [Journal Article] Spatiotemporal regulation of T cell costimulation by TCR-CD28 microclusters through protein kinase C θ translocation (2008)
  • Author(s): Yokosuka T., Kobayashi, W., Sakata-Sogawa K., Hashimoto-Tane, A., Dustin, M.L., Tokunaga. M., Saito, T.
  • Journal Title: Immunity 29 Pages: 589-301
  • Peer Reviewed
• [Journal Article] LFA-1 decreases the antigen dose for T cell activation in vivo (2008)
  • Author(s): Wang Y, Shibuya K, Yamashita Y, Shirakawa J, Shibata K, Kai H, Yokosuka T, Saito T, Honda S, Tahara-Hanaoka S, Shibuya A.
  • Journal Title: Int. Immunol. 20 Pages: 1119-1127
  • NAID: 10022599219
  • Peer Reviewed
• [Journal Article] Genetic analysis reveals an intrinsic property of the germinal center B cells to generate A:T mutations (2008)
  • Author(s): Ouchida R, Ukai A, Mori H, Kawamura K, Dolle ME, Tagawa M, Sakamoto A, Tokuhisa T, Yokosuka T, Saito T, Yokoi M, Hanaoka F, Vijg J, Wang JY.
  • Journal Title: DNA Repair 7 Pages: 1392-1398
  • Peer Reviewed
• [Journal Article] LFA-1 decreases the antigen dose for T cell activation in vivo (2008)
  • Author(s): Wang, Y.
  • Journal Title: International Immunology 20 Pages: 1119-1127
  • Peer Reviewed
• [Journal Article] Genetic analysis reveals an intrinsic property of the germinal center B cells to generate A : T mutations (2008)
  • Author(s): Ouchida, R.
  • Journal Title: DNA Repair (Amst.) 7 Pages: 1392-1398
  • Peer Reviewed
• [Journal Article] Spatiotemporal regulation of T cell costimulation by TCR-CD28 microclusters through protein kinase C θ translocation (2008)
  • Author(s): Yokosuka, T.
  • Journal Title: Immunity 29 Pages: 589-601
  • Peer Reviewed
• [Journal Article] T細胞活性化時のTCRとシグナル伝達分子の動態 (2008)
  • Author(s): 横須賀忠
  • Journal Title: 臨床免疫・アレルギー科(Clinical Immunology & Allergology) 50 Pages: 247-254
  • Peer Reviewed
• [Journal Article] Cloning of B cell-specific membrane tetraspanning molecule BTS possessing B cell proliferation-inhibitory function (2007)
  • Author(s): Suenaga T, Arase H, Yamasaki S, Kohno M, Yokosuka T, Takeuchi A, Hattori T, Saito T.
  • Journal Title: Eur. J. Immunol. 37 Pages: 3197-3207
  • Peer Reviewed
• [Journal Article] Cloning of B-cell-specific membrane tetraspanning molecule BTS possessing B cell proliferation-inhibitory function (2007)
  • Author(s): Suenaga, T.
  • Journal Title: European Journal of Immunology 37 Pages: 3197-3207
  • Peer Reviewed
• [Journal Article] 免疫シナプスを構成するTCRマイクロクラスターとT細胞活性化機構 (2007)
  • Author(s): 横須賀 忠
  • Journal Title: Annual Review免疫2008 Pages: 1-11
• [Presentation] Dynamic Regulation of T Cell Co-stimulation by TCR-CD28 Microclusters (2009)
  • Author(s): Yokosuka, T.
  • Organizer: LIAI-RCAI Joint Workshop 2009-Regulation of Lymphocyte Function and Immune Responses
  • Place of Presentation: 横浜
  • Year and Date: 2009-01-07
• [Presentation] T細胞の副刺激を制御する免疫シナプスの領域の同定/Identification of a region in immunological synapse critical for T cell co-stimulation (2008)
  • Author(s): Yokosuka, T.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] CRTAMはCD8α+樹状細胞との相互作用を介してCD8+T細胞の増殖を制御する。/CRTAM regulate CD8+ T cell proliferation in regional lymph nodes through the interaction with CD8α+dendritic cell (2008)
  • Author(s): Takeuchi, A.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] CD3ζGFPノックイン細胞を用いたTCRミクロクラスターの定量的な解析/Quantitative analysis of TCR microclusters in CD3zetaGFP knock-in T cells (2008)
  • Author(s): 橋本彰子(多根)
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] Visualization of signaling complex upon T cell activation (2008)
  • Author(s): Yokosuka, T.
  • Organizer: The 2nd joint symposium between immunology and imaging, WIP-iFReC,
  • Place of Presentation: 大阪
  • Year and Date: 2008-08-28
• [Presentation] Dynamic Regulation of T Cell Co-stimulation by TCR-CD28 Microclusters (2008)
  • Author(s): Saito, T.
  • Organizer: RCAI-JSI International Symposium on Immunology 2008
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-26
• [Presentation] T細胞の副刺激を制御する免疫シナプスの領域の同定/ Identification of a region in immunological synapse critical for T cell co-stimulation (2008)
  • Author(s): Yokosuka, T., Sogawa-Sakata, K., Tane-Hashimoto, A., Tokunaga, M., Dustine, ML., Saito, T.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] T cell recognition and activation through TCR microclusters (2007)
  • Author(s): Saito, T.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] TCRミクロクラスターにおけるリピッドラフトの動態/Mobilization of Lipid raft at Immunological Synapse (2007)
  • Author(s): 橋本(多根) 彰子
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] CRTAM confers retention in lymph nodes and efficient delivery to effector sites of antigen-specific CD8+T cells (2007)
  • Author(s): Takeuchi, A.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] TCR-CD28マイクロクラスターとc-SMACによるT細胞活性化の時空間的制御/Spatiotemporal regulations of T cell activation by a c-SMAC and TCR-CD28-microclusters (2007)
  • Author(s): Yokosuka, T.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] 新規B細胞特異的4回膜貫通型分子BTSは、mTORシグナル経路を介して細胞サイズとB細胞分化を制御する/A newly cloned B cell-specific tetramembrane spanning molecule BTS regulates cell size through mTOR pathway and B cell development (2007)
  • Author(s): Suenaga, T.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] Spatiotemporal regulation of lymphocyte activation-Signalsome,TCR-microcluster- (2007)
  • Author(s): Yokosuka, T.
  • Organizer: National Academy of Engineering 2007 Japan-America Frontiers of Engineering Symposium(第7回日米先端工学シンポジウム)
  • Place of Presentation: California,USA
  • Year and Date: 2007-11-05
• [Presentation] Spatiotemporal regulation of T cell activation by TCR-CD28-microclusters (2007)
  • Author(s): Yokosuka, T.
  • Organizer: 13^<th>International Congress of Immunology
  • Place of Presentation: Rio de Janeiro,Brazil
  • Year and Date: 2007-08-21
• [Presentation] Spatiotemporal regulation of T cell activation by TCR-CD28-microclusters (2007)
  • Author(s): Yokosuka, T.
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: Colorado,USA
  • Year and Date: 2007-06-26
• [Presentation] TCR-CD28マイクロクラスターによるT細胞活性化の時空間的制御 (2007)
  • Author(s): 横須賀 忠
  • Organizer: 第17回Kyoto T Cell Coference(KTCC)学術集会
  • Place of Presentation: 京都
  • Year and Date: 2007-06-15
• [Presentation] Immunological SynapseにおけるLipid raftの動態 (2007)
  • Author(s): 多根 彰子
  • Organizer: 第17回Kyoto T Cell Coference(KTCC)学術集会
  • Place of Presentation: 京都
  • Year and Date: 2007-06-15
• [Presentation] Spatiotemporal regulation of T cell activation by TCR-CD28-microclusters (2007)
  • Author(s): Yokosuka, T.
  • Organizer: 第7回日本蛋白質科学会年会(The7^<th>Annual Meeting of Protein Science Society of Japan)
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-25
• [Presentation] TCR-CD28マイクロクラスターとc-SMACによるT細胞活性化の時空間的制御Spatiotemporal regulations of T cell activation by a c-SMAC and TCR-CD28-microclusters (2007)
  • Author(s): Yokosuka, T., Sakata-Sogawa, Hashimoto-Tane, A., Tokunaga, M., Dustin, ML. and Saito, T.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Spatiotemporal regulation of lymphocyte activation: Signalsome, TCR-microcluster (2007)
  • Author(s): Yokosuka, T.
  • Organizer: National Academy of Engineering 2007 Japan-America Frontiers of Engineering Symposium 第7回日米先端工学シンポジウム
  • Place of Presentation: パロアルト
• [Presentation] Spatiotemporal regulation of T cell activation by TCR-CD28-microclusters (2007)
  • Author(s): Yokosuka, T., Sakata-Sogawa, K. Kobayashi, W., Hiroshima, M., Hashimoto-Tane, A., Tokunaga, M., Dustine M.L. and Saito, T. (Minisymposium) (20070821)
  • Organizer: 13th International Congress of Immunology
  • Place of Presentation: リオデジャネイロ
• [Presentation] TCR-CD28-マイクロクラスターによるT細胞活性化の時空間的制御 (2007)
  • Author(s): 横須賀忠
  • Organizer: 第7回日本蛋白質科学会年会
  • Place of Presentation: 仙台
• [Presentation] Spatiotemporal regulation of T cell activation by TCR-CD28-microclusters (2007)
  • Author(s): Yokosuka, T.
  • Organizer: 第10回国際細胞膜研究フォーラム
  • Place of Presentation: 京都
• [Book] T細胞活性化時のTCRとシグナル伝達分子の動態:臨床免疫・アレルギー科50巻3号 2008年9月号 (2008)
  • Author(s): 横須賀忠
  • Publisher: 科学評論社
• [Book] 免疫シナプスを構成するTCRマイクロクラスターと T 細胞活性化機構:Annual Review 2008 2007年11月20日 (2007)
  • Author(s): 横須賀忠
  • Publisher: 中外医学社
• [Book] T細胞受容体マイクロクラスター-T細胞活性化を制御するシグナルソームの発見-:感染炎症免疫37巻2号 (2007)
  • Author(s): 横須賀忠
  • Publisher: 医薬の門社
• [Remarks] ホームページ等
  • URL: http://web.rcai.riken.jp/en/labo/signaling/index.html