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2008 Fiscal Year Annual Research Report

T細胞の抗原認識と活性化の時空間制御の解析

Research Project

Project/Area Number 19109005
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

斉藤 隆  The Institute of Physical and Chemical Research, 免疫シグナル研究グループ, グループディレクター (50205655)

Co-Investigator(Kenkyū-buntansha) 横須賀 忠  独立行政法人理化学研究所, 免疫シグナル研究グループ, 上級研究員 (10359599)
Keywords免疫学 / シグナル伝達 / T細胞 / 抗原認識 / イメージング
Research Abstract

T細胞の抗原認識と活性化のユニットであると考えられるTCRミクロクラスター(TCR-MC)の形成とその機能と制御機構の解析を目指した。CD3ζ-knock inマウスを作製して、そのT細胞を用いることで、生理的条件下でTCR-MCが同様に誘導形成されることが判明し、その定量的解析が可能となった。
抗原認識におけるTCR-MCの役割を解析するために、非自己と自己ペプチドをcovalent結合させたMHCを比率を変えて資質二重膜の上に発現させて解析した結果、アゴニストペプチドで形成されるミクロクラスターには自己ペプチドが共存せず、CD4+T細胞では自己ペプチドの関与は否定的であることが示唆された。
TCR-MCによるシグナルソームと活性化制御の解析に関しては、T細胞活性化に不可欠な副刺激シグナルおよび脂質ラフトとTCR-MCとの関係を解析した。CD28を介する副刺激受容体を介するシグナル伝達系の、TCRミクロクラスターとの動態の関係を解析した。活性化初期では、CD28もTCR-MCに集まりPKCθをリクルートして会合し、免疫シナプス形成後には、シナプスの中心にCD28-PKCθが集結して、副刺激シグナルの維持を行い、T細胞活性化維持に貢献することが明らかになった。
一方、LAT,Lck,Lynを含む異なるラフトマーカーを用いることによって、脂質ラフトはTCR-MCと同じようにはクラスターを形成しないことが判明し、活性化シグナルはラフトの凝集を介しては誘導されず、蛋白相互作用によると思われる。

  • Research Products

    (38 results)

All 2009 2008

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (20 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Fc receptor c-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils2009

    • Author(s)
      Hida, S.
    • Journal Title

      Nat. Immunol. 10

      Pages: 214-222

    • Peer Reviewed
  • [Journal Article] C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia2009

    • Author(s)
      Yamasaki, S.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

    • Peer Reviewed
  • [Journal Article] Differential trafficking of c-Src, Lyn, c-Yes, and Fyn is specified by the state of palmitoylation in the SH4 domain2009

    • Author(s)
      Sato, I.
    • Journal Title

      J. Cell Sci.

    • Peer Reviewed
  • [Journal Article] Regulation of NF-kappa B-dependent T cell activation and development by MEKK32009

    • Author(s)
      Shinohara, H.
    • Journal Title

      Int. Immunol.

    • Peer Reviewed
  • [Journal Article] Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease2009

    • Author(s)
      Sato, K.
    • Journal Title

      Blood

    • Peer Reviewed
  • [Journal Article] Nuclear localization of Src-family tyrosine kinases is required for growth factor-induced euchromatinization2009

    • Author(s)
      Takahashi, A.
    • Journal Title

      Exp. Cell Res.

    • Peer Reviewed
  • [Journal Article] A lysosomal protein negatively regulate surface T cell antigen receptor expression by promoting CD3ζ degradation2008

    • Author(s)
      Ouchida, R.
    • Journal Title

      Immunity 29

      Pages: 33-43

    • Peer Reviewed
  • [Journal Article] Thymic selection determines γ δ T cell effector fate : antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon γ2008

    • Author(s)
      Jensen, K. D.
    • Journal Title

      Immunity 29

      Pages: 90-100

    • Peer Reviewed
  • [Journal Article] Cell type-specific regulation of ITAM-mediated NF-κB activation by the adaptors, CARMA1 and CARD92008

    • Author(s)
      Hara, H.
    • Journal Title

      J. Immunol. 181

      Pages: 918-930

    • Peer Reviewed
  • [Journal Article] LFA-1 decreases the antigen dose for T cell activation in vivo2008

    • Author(s)
      Wang, Y.
    • Journal Title

      Int. Immunol. 20

      Pages: 1119-1127

    • Peer Reviewed
  • [Journal Article] Genetic analysis reveals an intrinsic property of the germinal center B cells to generate A : T mutations2008

    • Author(s)
      Ouchida, R.
    • Journal Title

      DNA Repair (Amst) 7

      Pages: 1392-1398

    • Peer Reviewed
  • [Journal Article] Selective impairment of FcεRI-mediated allergic reaction in Gadsdeficient mice2008

    • Author(s)
      Yamasaki, S.
    • Journal Title

      Int. Immunol. 20

      Pages: 1289-1297

    • Peer Reviewed
  • [Journal Article] Mincle is an ITAM-coupled activating receptor that senses damaged cells2008

    • Author(s)
      Yamasaki, S.
    • Journal Title

      Nat. Immunol. 9

      Pages: 1179-1188

    • Peer Reviewed
  • [Journal Article] Spatiotemporal regulation of T cell costimulation by TCR-CD28 microclusters and protein kinase C θ translocation2008

    • Author(s)
      Yokosuka, T.
    • Journal Title

      Immunity 29

      Pages: 589-601

    • Peer Reviewed
  • [Journal Article] Essential role of Rap signal in pre-TCR-mediated β-selection checkpoint in αβ T cell development2008

    • Author(s)
      Kometani, K.
    • Journal Title

      Blood 112

      Pages: 4565-4573

    • Peer Reviewed
  • [Journal Article] Early development of human hematopoietic and acquired immune systems in new born NOD/Scid/Jak3null mice intrahepatic engrafted with cord blood-derived CD34+ cells2008

    • Author(s)
      Okada, S.
    • Journal Title

      Int. J. Hematol. 88

      Pages: 476-482

    • Peer Reviewed
  • [Presentation] Recognition of damaged self and non-self pathogens by ITAM-coupled C-type lectin, Mincle2009

    • Author(s)
      Yamasaki, S and Saito, T.
    • Organizer
      World Immune Regulation Meeting-III
    • Place of Presentation
      Davos, Switzerland
    • Year and Date
      2009-03-23
  • [Presentation] C型レクチン Mincle による自己・非自己リガンドの認識とその意義2009

    • Author(s)
      山崎晶
    • Organizer
      第18回東京免疫フォーラム
    • Place of Presentation
      東京
    • Year and Date
      2009-03-12
  • [Presentation] ITAM受容体による免疫系の形成・維持と生体防御の制御機構2009

    • Author(s)
      山崎晶
    • Organizer
      慶応医学会例会
    • Place of Presentation
      東京
    • Year and Date
      2009-02-18
  • [Presentation] Self and non-self recognition by ITAM-coupled C-type lectin receptor, Mincle2009

    • Author(s)
      Yamasaki, S.
    • Organizer
      The 2^<nd> International Symposium of WPI Immunology Frontier Research Center
    • Place of Presentation
      大阪
    • Year and Date
      2009-02-13
  • [Presentation] Dynamic assembly of signaling unit for antigen recognition and activation of immune cells2009

    • Author(s)
      Saito, T.
    • Organizer
      Symposium on Meso Control of the cells, by the cells, for the cells
    • Place of Presentation
      京都
    • Year and Date
      2009-01-27
  • [Presentation] Dynamic regulation of T cell co-stimulation by TCR-CD28 microclusters2009

    • Author(s)
      Yokosuka, T.
    • Organizer
      LIAI-RCAI Joint Workshop 2009
    • Place of Presentation
      横浜
    • Year and Date
      2009-01-07
  • [Presentation] C-type lectin Mincle is an ITAM-coupled activating receptor sensing damaged cells2008

    • Author(s)
      Yamasaki, S.
    • Organizer
      FASEB Summer Research Conferences
    • Place of Presentation
      New Haven, CT、USA
    • Year and Date
      20080803-20080808
  • [Presentation] Mincle is an ITAM-coupled activating receptor that senses damaged cells2008

    • Author(s)
      Yamasaki, S.
    • 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] C-type lectin Mincle is an ITAM-coupled activating receptor sensing damaged cells2008

    • Author(s)
      Yamasaki, S.
    • 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] Identification of a region in immunological synapse critical for T cell co-stimulation2008

    • 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 regulate CD8^+ T cell proliferation in regional lymph nodes through the interaction with CD8α^+ dendritic cell2008

    • 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] Quantitative analysis of TCR microclusters in CD3zetaGFP knock-in T cells2008

    • Author(s)
      Hashimoto-Tane, 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] pre-TCRα-chain knock-in mice lacking charged residues2008

    • Author(s)
      Ishikawa, E.
    • 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] Dynamic Regulation of Immunological Synapse and T cell Activation2008

    • Author(s)
      Saito, T.
    • Organizer
      17th Annual Meeting of Bioimaging Society
    • Place of Presentation
      千葉
    • Year and Date
      2008-10-31
  • [Presentation] Dynamic regulation of TCR- and costimulatory signals via microclusters2008

    • Author(s)
      Saito, T.
    • Organizer
      Cantoblanco Workshops on Biology, Initiation of Antigen Receptor Signaling
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      2008-10-22
  • [Presentation] Macrophage-inducible C-type lectin is an ITAM-coupled activating receptor that senses damaged cells2008

    • Author(s)
      Saito, T.
    • Organizer
      第10回国際樹状細胞シンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2008-10-08
  • [Presentation] C-type lectin Mincle is an ITAM-coupled activating receptor sensing damaged cells2008

    • Author(s)
      Saito, T.
    • Organizer
      The 8th Awaji International Forum of Infection and Immunity
    • Place of Presentation
      淡路
    • Year and Date
      2008-09-09
  • [Presentation] 免疫応答の始まりと維持の分子機構-T細胞活性化のダイナミズム-2008

    • Author(s)
      斉藤隆
    • Organizer
      日本免疫学会免疫サマースクール2008
    • Place of Presentation
      南あわじ
    • Year and Date
      2008-08-25
  • [Presentation] Dynamic Regulation of T Cell Co-stimulation by TCR-CD28 Microclusters2008

    • 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細胞初期分化におけるNFκBの役割2008

    • Author(s)
      山崎晶
    • Organizer
      第18回 Kyoto T Cell Conference 学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-06-13
  • [Patent(Industrial Property Rights)] 糖鎖認識受容体の新規用途2008

    • Inventor(s)
      斉藤隆, 山崎晶
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Number
      特願2008-186570
    • Filing Date
      2008-07-17
  • [Patent(Industrial Property Rights)] 糖鎖認識受容体の新規用途2008

    • Inventor(s)
      斉藤隆, 山崎晶, 他
    • Industrial Property Rights Holder
      理化学研究所,千葉大学
    • Industrial Property Number
      特願2008-285948
    • Filing Date
      2008-11-06

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Published: 2010-06-11   Modified: 2016-04-21  

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