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2007 Fiscal Year Annual Research Report

自己識別と活性化制御

Planned Research

Project AreaImmunological Self Recognition and its Disorders
Project/Area Number 19059013
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) 黒崎 知博  独立行政法人理化学研究所, 分化制御研究グループ, グループディレクター (50178125)
Keywordsシグナル伝達 / 抗原受容体 / リンパ球活性化 / 自己識別 / 自己反応性制御
Research Abstract

免疫系における自己識別・反応性を担うシグナル伝達と制御機構を明らかにするため、T細胞の自己成分認識と自己反応性による制御、B細胞における自己反応性の抑制と細胞生存のためのシグナル制御の分子機構、を解析している。1.自己抗原認識のT細胞の活性化への影響を調べるために、外来抗原(チトクロムc)および数種の自己抗原ペプチドを、I-Eβ鎖に直接結合させた単一ペプチド・MHC分子をGPI結合型として作製し、細胞に遺伝子導入して、MHC/ペプチド-GPIの単一分子を単離した。これらの単一分子のT細胞による認識・活性化能を、これらを含むplanar membraneでコートしたビーズを用いて解析した。その結果、外来ペプチドのMHC/ペプチド-GPI単一分子はフリーペプチド同様に活性のあることが判明した。また自己ペプチド単一分子は、もはや外来ペプチドには反応できないことが判明した。これらの脂質二重膜を用いて自己・外来抗原濃度を変化させた際のTCRミクロクラスター形成と活性化を解析中である。2.BCRを介するトニックシグナルは末梢Bリンパ球の生存に必須と考えられている。BCRシグナル分子群、PLCγ-2, STIM1, Rukのトニックシグナルにおける寄与を検索するため、トニックシグナルを供与できるモデルレセプターLMP2-Tgマウスとこれらシグナル分子の欠損マウスを交配した。結果PLCγ-2欠損マウスではB細胞分化が初期段階で阻害され、PLCγ-2がトニックシグナルに必須であることが判明した。更にPLCγ-2の下流で重要なシグナル径路を検索し、Ras径路のgain-of-function変異がrescueすることより、PLCγ-2→Rasの径路のトニックシグナルにおける重要性が示唆された。自己不応答性の検索に関してはモデルBCR系であるHELシステムとの交配が完了し、現在解析中である。

  • Research Products

    (28 results)

All 2008 2007

All Journal Article (9 results) (of which Peer Reviewed: 8 results) Presentation (19 results)

  • [Journal Article] Differential contribution of three activating IgG Fc receptors (FcγRI,FcγRIII and FcγRIV) to IgG2a- and IgG2b-induced autoimmune hemolytic anemia in mice.2008

    • Author(s)
      Baudino, L.
    • Journal Title

      J. Immunol. 180

      Pages: 1948-1953

    • Peer Reviewed
  • [Journal Article] The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation.2007

    • Author(s)
      Suzuki, J-I.
    • Journal Title

      Blood 109

      Pages: 168-175

    • Peer Reviewed
  • [Journal Article] (Molecular basis for pre-TCR-mediated autonomous signaling.2007

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

      Trends. Immunol. 28

      Pages: 39-43

  • [Journal Article] LAT and NTAL mediate immunoglobulin E-induced sustained extracellular signal-regulated kinase activation critical for mast cell survival.2007

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

      Mol. Cel. Biol. 27

      Pages: 4406-4415

    • Peer Reviewed
  • [Journal Article] The adaptor protein CARD9 is essential for activation of myeloid cells through ITAM-associated and Toll-like receptors.2007

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

      Nature Immunol. 8

      Pages: 619-629

    • Peer Reviewed
  • [Journal Article] TLR2 directly triggers Th1 effector functions.2007

    • Author(s)
      Imanishi T.
    • Journal Title

      J. Immunol. 178

      Pages: 6715-6719

    • Peer Reviewed
  • [Journal Article] Diverging signaling events control the pathway of GPVI downregulation in vivo.2007

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

      Blood 110

      Pages: 529-535

    • Peer Reviewed
  • [Journal Article] Construction of an open-access database that integrates cross-reference information from the transcriptome and proteome of immune cells.2007

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

      Bioinformatics 23

      Pages: 2934-2941

    • 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

      Eur. J. Immunol. 37

      Pages: 3197-3207

    • Peer Reviewed
  • [Presentation] Imaging of initiation of T cell activation2008

    • Author(s)
      Saito, T.
    • Organizer
      Kick-off Symposium of WPI IFReC, Immunology and Imaging
    • Place of Presentation
      大阪
    • Year and Date
      2008-03-28
  • [Presentation] Spatiotemporal regulation of T cell activation and co-stimulation by microclusters2008

    • Author(s)
      Saito, T.
    • Organizer
      The First iCeMS International Symposium: The Eleventh Membrane Research Forum
    • Place of Presentation
      京都
    • Year and Date
      2008-02-22
  • [Presentation] Differential cellular adaptors mediating innate and adaptive immunity2008

    • Author(s)
      Saito, T.
    • Organizer
      Hepatic Inflammation and Immunity 2008
    • Place of Presentation
      Galveston, USA
    • Year and Date
      2008-01-25
  • [Presentation] CRTAM regulates retention of T cells within lymph node and delivery to effecter tissues2008

    • Author(s)
      Saito, T.
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Keystone, USA
    • Year and Date
      2008-01-16
  • [Presentation] Activation-stage-specific differential functions of toll-like receptors on T cells for T cell activation and survival.2007

    • Author(s)
      Imanishi, T.
    • Organizer
      The 20th Naito Conference-Innate Immunity in Medicine and Biology [III]
    • Place of Presentation
      葉山
    • Year and Date
      20071109-12
  • [Presentation] Dynamic regulation of T cell activation through TCR micloclusters2007

    • Author(s)
      Saito, T.
    • Organizer
      13th International Congress of Immunology
    • Place of Presentation
      Rio de Janeiro, Brazil
    • Year and Date
      20070821-20070825
  • [Presentation] Differential regulation of pre-TCR- and αβTCR-mediated signaling2007

    • Author(s)
      Yamasaki, S.
    • Organizer
      FASEB Summer Research Conferences-Signal Transduction in the Immune System
    • Place of Presentation
      Snowmass, USA
    • Year and Date
      20070623-28
  • [Presentation] TCRミクロクラスターによる抗原認識と活性化の動的制御2007

    • Author(s)
      斉藤 隆
    • Organizer
      BMB2007第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-13
  • [Presentation] TLR3/9 directly augments naive/memory CD4+ T cell survival independently of Myd88/IRAK-42007

    • Author(s)
      Imanishi, 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
      2007-11-22
  • [Presentation] T cell recognition and activation through TCR microclusters2007

    • 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-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2007

    • Author(s)
      横須賀 忠
    • 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] Differential regulation of innate immune signaling through CARMA1 and CARD9 adaptors.2007

    • Author(s)
      Hara, H.
    • 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] CARD 9-mediated innate signaling in myeloid cells2007

    • Author(s)
      Saito, T.
    • Organizer
      The 20th Naito Conference-Innate Immunity in Medicine and Biology [III]
    • Place of Presentation
      葉山
    • Year and Date
      2007-10-10
  • [Presentation] Physiological role of CRTAM expression in vivo immunity2007

    • Author(s)
      Takeuchi, A.
    • Organizer
      13th International Congress of Immunology
    • Place of Presentation
      Rio de Janeiro, Brazil
    • Year and Date
      2007-08-23
  • [Presentation] Spatiotemporal regulation of T cell activation by TCR-CD28-microclusters2007

    • Author(s)
      Yokosuka, T.
    • Organizer
      13th International Congress of Immunology
    • Place of Presentation
      Rio de Janeiro, Brazil
    • Year and Date
      2007-08-21
  • [Presentation] Positive selectionに選択的なシグナル伝達経路の解析2007

    • Author(s)
      山崎 晶
    • 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] Initiation and sustenance of T cell activation by TCR microclusters2007

    • Author(s)
      Saito, T.
    • Organizer
      4th International Leukocyte Signal Transduction Workshop
    • Place of Presentation
      Rhodes, Greece
    • Year and Date
      2007-06-04
  • [Presentation] TCR microclusters and co-stimulation for T cell activation2007

    • Author(s)
      Saito, T.
    • Organizer
      EMBO Conference Series on "Signaling in the immune system"
    • Place of Presentation
      Siena, Italy
    • Year and Date
      2007-05-26
  • [Presentation] Spatiotemporal regulation of T cell activation by TCR-CD28-microclusters2007

    • Author(s)
      Yokosuka, T.
    • Organizer
      第7回日本蛋白質科学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2007-05-25

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Published: 2010-02-04   Modified: 2016-04-21  

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