The microsynapse is an essential structure for T cell activation

• Project/Area Number: 24590591
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: HASHIMOTO-TANE Akiko 独立行政法人理化学研究所, 統合生命医科学研究センター, 研究員 (10415226)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: T細胞 / 免疫シナプス / T細胞受容体 / 受容体クラスター / インテグリン / ミオシン / 蛍光イメージング / 全反射顕微鏡 / 免疫シグナル / ミオシンII / 免疫 / シグナル伝達 / アクチン / 受容体シグナル / モーター分子

Outline of Final Research Achievements

In this study, we tried to reveal the mechanism for translation of TCR stimulation strength through quantitative imaging analysis of TCR microcluster (TCR-MC), which is a minimum assemble to start T cell activation. We performed proteome analysis and fluorescent imaging, and found that each TCR-MC was transiently bordered by a ring of focal adhesion molecules during the initial stage of T cell activation. The ring structure, which we named the microsynapse, is composed of LFA-1 and focal adhesion molecules such as paxillin, Pyk2 and the core structure of the TCR-MC. The microsynapse is supported by integrin outside-in signals, F-actin and myosin II activity. Perturbation of the microsynapse induced impairment of TCR-MC formation, reduced SLP76 recruitment, and resulted in impaired cellular signaling and function in vitro and in vivo. Thus, the microsynapse supports weak TCR response through integrin outside-in signals and is a critical structure for T cell activation.

Research Products

• [Journal Article] Nucleic acid sensing by T cells initiates Th2 cell differentiation. (2014)
  • Author(s): Imanishi T, Ishihara C, Badr Mel S, Hashimoto-Tane A, Kimura Y, Kawai T, Takeuchi O, Ishii KJ, Taniguchi S, Noda T, Hirano H, Brombacher F, Barber GN, Akira S, Saito T.
  • Journal Title: Nature Communications Volume: 5 Pages: 3566-3566
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Programmed cell death-1 forms negative costimulatorymicroclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2 (2012)
  • Author(s): Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tani A, Azuma M, Saito T
  • Journal Title: J Exp Med Volume: 209 Issue: 6 Pages: 935-945
  • DOI: 10.1084/jem.20112741
  • Peer Reviewed
• [Presentation] “Microsynapse” composed of focal adhesion molecules surrounding TCR microcluster is essential for T cell activation (2015)
  • Author(s): Hashimoto-Tane, A., Sakuma, M., Yokosuka, T., Saito, T
  • Organizer: 2015 Keystone Symposia Conference D3: T Cells: Regulation and Effector Function
  • Place of Presentation: アメリカ、ユタ州、スノーバードリゾート
  • Year and Date: 2015-03-30
• [Presentation] T細胞活性化開始点であるT細胞受容体ミクロクラスターを支える構造体ミクロシナプスの解析 (2015)
  • Author(s): 橋本ー多根 彰子、横須賀忠、斉藤隆
  • Organizer: 88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-19
• [Presentation] “Microsynapse” structure supporting TCR microclusters augments T cell activation, (2014)
  • Author(s): Hashimoto-Tane, A., Yokosuka, T., Saito, T
  • Organizer: 第43回日本免疫学会学術総会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-12-11
• [Presentation] Subcellular imaging of the E3 ubiquitin ligases, c-Cbl and Cbl-b, to control T cell activation signals through ubiquitin clustering at TCR microclusters (2014)
  • Author(s): Yokosuka, T., Hashimoto-Tane, A., Saito, T
  • Organizer: 第43回日本免疫学会学術総会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-12-11
• [Presentation] Arp2/3 complex-mediated actin-nucleation supports T cell receptor microcluster (2013)
  • Author(s): Hashimoto-Tane, A., Yokosuka, T., Saito, T
  • Organizer: 第42回日本免疫学会
  • Place of Presentation: Makuhari Messe, Chiba
• [Presentation] Dynamic and cytoskeletal regulation of T cell activation (2013)
  • Author(s): Saito, T., Yokosuka, T., Hashimoto-Tane, A.
  • Organizer: Michigan-RCAI Joint Workshop
  • Place of Presentation: Detroit, MC USA
• [Presentation] Regulation of T cell receptor signaling by cytoskeletal dynamics (2013)
  • Author(s): Hashimoto-Tane, A., Sakuma, M., Yokosuka, T., Saito, T
  • Organizer: The 5th Biennale RIKEN Joint Retreat “Behavior from Molecules, Cells to Organisms
  • Place of Presentation: YAMAHAリゾートつごもり(静岡県掛川市)
• [Presentation] Negative costimulatory microclusters inhibiting T cell-mediated inflammation (2013)
  • Author(s): Yokosuka, T., Hashimoto-Tane, A., Saito, T.
  • Organizer: JST-CREST International Symposium ”Frontiers in Immunology and Inflammation: from Molecules to Disease”
  • Place of Presentation: 一橋記念講堂(東京都千代田区)
• [Presentation] The movement of T cell receptor signaling molecules (2012)
  • Author(s): 多根(橋本) 彰子
  • Organizer: 実験研究者のための数理生物学サマーレクチャーコー ス第1回
  • Place of Presentation: 理化学研究所(神戸市中央区)
• [Book] 臨床免疫・ア レルギー科 (2013)
  • Author(s): 多根（橋本）彰子
  • Total Pages: 6
  • Publisher: 科学評論社
• [Book] 感染・炎症・免疫 (2012)
  • Author(s): 多根（橋本）彰子、斉藤 隆.
  • Total Pages: 4
  • Publisher: 科学評論社