Self recognition and activation regulation

2011 Fiscal Year Final Research Report

• Project Area: Immunological Self Recognition and its Disorders
• Project/Area Number: 19059013
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: SAITO Takashi 独立行政法人理化学研究所, 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): KUROSAKI Tomohiro 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)
• Project Period (FY): 2007 – 2011
• Keywords: 自己抗原 / 自己認識 / T細胞 / 活性化シグナル / 獲得免疫 / ミクロクラスター / planar bilayer

Research Abstract

T cells are activated through forming TCR-microclusters (MC) upon antigen recognition. Self-peptides cannot induce TCR-MCs, and only the agonist peptides are accumulated into TCR-MCs when agonist and self-peptides are mixed. Thymocytes form TCR-MCs upon self-peptide recognition, and only the strong-stimulus of negative selecting peptides induces cSMAC formation. We clarified spatiotemporal regulation by positive (CD28) and negative (CTLA-4) costimulation and cytoskeletal regulation.

Research Products

• [Journal Article] A motif in the V3 domain of the kinase PKC-θ determines its localization in the immunological synapse and functions in T cells via association with CD28 (2011)
  • Author(s): Kong K-F, et al.
  • Journal Title: Nat. Immunol. Volume: 21 Pages: 1105-12
  • Peer Reviewed
• [Journal Article] Nanocluster formation: More with memory (2011)
  • Author(s): Saito T.
  • Journal Title: Immunity Volume: 35 Pages: 318-320
  • Peer Reviewed
• [Journal Article] CIN85 regulates the canonical NF-кB pathway and subsequent B cell responses (2011)
  • Author(s): Kometani K, Yamada T, Sasaki Y, Yokosuka T, Saito T, Rajewsky K, Ishiai M, Hikida M, Kurosaki T.
  • Journal Title: J. Exp. Med. Volume: 208 Pages: 1447-1457
  • Peer Reviewed
• [Journal Article] Dynein-driven transport of T cell receptor microclusters regulates immune synapse formation and T cell activation (2011)
  • Author(s): Hashimoto-Tane A, Yokosuka T, Sakata-Sogawa K, Sakuma M, Ishihara C, Tokunaga M, Saito T.
  • Journal Title: Immunity Volume: 34 Pages: 919-931
  • Peer Reviewed
• [Journal Article] Induction of colonic regulatory T cells by indigenous clostridium species (2011)
  • Author(s): Atarashi K, et al.
  • Journal Title: Science Volume: 331 Pages: 337-341
  • Peer Reviewed
• [Journal Article] Dynamic regulation of T cell activation and co-stimulation through TCR-microclusters (2010)
  • Author(s): Saito T, Yokosuka T, Hashimoto-Tane A.
  • Journal Title: FEBS Lett. Volume: 584 Pages: 4865-4871
  • Peer Reviewed
• [Journal Article] Germ-line elimination of electric charge on pre-T-cell receptor (TCR) impairs autonomous signaling for beta-selection and TCR repertoire formation (2010)
  • Author(s): Ishikawa E, et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 19979-19984
  • Peer Reviewed
• [Journal Article] Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation (2010)
  • Author(s): Yokosuka T, Kobayashi W, Takamatsu M, Sakata-Sogawa K, Zeng H, Hashimoto-Tane A, Yagita H, Tokunaga M, Saito T.
  • Journal Title: Immunity Volume: 33 Pages: 326-339
  • Peer Reviewed
• [Journal Article] T cell receptor-microclusters critical for T-cell activation are formed independently of lipid raft clustering (2010)
  • Author(s): Hashimoto-Tane A, Yokosuka T, Ishihara C, Sakuma M, Kobayashi W, Saito T.
  • Journal Title: Mol. Cel. Biol. Volume: 30 Pages: 3421-3429
  • Peer Reviewed
• [Journal Article] Dectin-2 recognition of α-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans (2010)
  • Author(s): Saijo S, et al.
  • Journal Title: Immunity Volume: 32 Pages: 681-691
  • Peer Reviewed
• [Journal Article] CRTAM confers late-stage activation of CD8^+ T cells to regulate retention within lymph node (2009)
  • Author(s): Takeuchi A, Itoh Y, Takumi A, Ishihara C, Arase N, Yokosuka T, Koseki H, Yamasaki S, Takai Y, Miyoshi J, Ogasawara K, Saito T.
  • Journal Title: J. Immunol. Volume: 183 Pages: 4220-4228
  • Peer Reviewed
• [Journal Article] Dynamic regulation of T-cell costimulation through TCR-CD28 microclusters (2009)
  • Author(s): Yokosuka T, Saito T.
  • Journal Title: Immunol. Rev. Volume: 229 Pages: 27-40
  • Peer Reviewed
• [Journal Article] CARD9 versus CARMA1 in innate and adaptive immunity. (2009)
  • Author(s): Hara H, Saito T.
  • Journal Title: Trends Immunol. Volume: 30 Pages: 234-242
  • Peer Reviewed
• [Journal Article] C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia (2009)
  • Author(s): Yamasaki S, Matsumoto M, Takeuchi O, Matsuzawa T, Ishikawa E, Sakuma M, Tateno H, Uno J, Hirabayashi J, Mikami Y, Takeda K, Akira S, Saito T.
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 10 Pages: 1897-1902
  • Peer Reviewed
• [Journal Article] Fc receptor γ-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils (2009)
  • Author(s): Hida S, et al.
  • Journal Title: Nat Immunol. Volume: 10 Pages: 214-222
  • Peer Reviewed
• [Journal Article] PLC-・2 is essential for formation and maintenance of memory B cells (2009)
  • Author(s): Hikida M, Casola S, Takahashi N, Kaji T, Takemori T, Rajewsky K, Kurosaki T.
  • Journal Title: J. Exp. Med. Volume: 206 Pages: 681-9
  • 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, Kobayashi W, Sakata-Sogawa, K, Takamatsu M, Hashimoto-Tane A, Dustin ML, Tokunaga M, Saito T.
  • Journal Title: Immunity. Volume: 29 Pages: 589-601
  • Peer Reviewed
• [Journal Article] Mincle is an ITAM-coupled activating receptor that senses damaged cells (2008)
  • Author(s): Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T.
  • Journal Title: Nat. Immunol. Volume: 9 Pages: 1179-1188
  • Peer Reviewed
• [Journal Article] Thymic selection determines γδ T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon γ (2008)
  • Author(s): Jensen KD, et al.
  • Journal Title: Immunity. Volume: 29 Pages: 90-100
  • Peer Reviewed
• [Journal Article] A lysosomal protein negatively regulate surface T cell antigen receptor expression by promoting CD3ζ-chain degradation (2008)
  • Author(s): Ouchida R, et al.
  • Journal Title: Immunity. Volume: 29 Pages: 33-43
  • Peer Reviewed
• [Journal Article] Erk kinases link pre-B cell receptor signaling to transcriptional events required for early B cell expansion (2008)
  • Author(s): Yasuda T, Sanjo H, Pages G, Kawano Y, Karasuyama H, Pouyssegur J, Ogata M, Kurosaki T.
  • Journal Title: Immunity Volume: 28 Pages: 499-508
  • Peer Reviewed
• [Journal Article] Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses (2008)
  • Author(s): Baba Y, Nishida K, Fujii Y, Hirano T, Hikida M, Kurosaki T.
  • Journal Title: Nat. Immunol. Volume: 9 Pages: 81-8
  • Peer Reviewed
• [Journal Article] Regulation of B- cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase (2008)
  • Author(s): Aiba Y, Kameyama M, Yamazaki T, Tedder TF, Kurosaki T.
  • Journal Title: Blood Volume: 111 Pages: 1497-1503
  • Peer Reviewed
• [Journal Article] TLR2 directly triggers Th1 effector functions (2007)
  • Author(s): Imanishi T, Hara H, Suzuki S, Suzuki N, Akira S, Saito T.
  • Journal Title: J. Immunol. Volume: 178 Pages: 6715-6719
  • Peer Reviewed
• [Journal Article] The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors (2007)
  • Author(s): Hara H, et al.
  • Journal Title: Nat. Immunol. Volume: 8 Pages: 619-629
  • Peer Reviewed
• [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, Ishikawa E, Sakuma M, Kanagawa O, Cheng AM, Malissen B, Saito T.
  • Journal Title: Mol. Cell. Biol. Volume: 27 Pages: 4406-4415
  • Peer Reviewed
• [Journal Article] I・B kinase ・-induced phosphorylation of CARMA1 contributes to CARMA1-Bc110-MALT1 complex formation in B cells (2007)
  • Author(s): Shinohara H, Maeda S, Watarai H, Kurosaki T.
  • Journal Title: J Exp Med. Volume: 204 Pages: 3285-3293
  • Peer Reviewed
• [Journal Article] Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2
  • Author(s): Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M, Saito T.
  • Journal Title: J. Exp. Med. Volume: (in press)
  • Peer Reviewed
• [Presentation] Negative regulation of TCR signaling by PD-1 microcluster (2012)
  • Author(s): Yokosuka, T., Saito, T.
  • Organizer: Keystone Symposia-Regulation of Lymphocyte Signaling
  • Place of Presentation: Keystone, CO. USA.
  • Year and Date: 2012-03-15
• [Presentation] Spatiotemporal regulation of T cell co-stimulation (2011)
  • Author(s): Saito, T., Yokosuka, T., Tane-Hashimoto, A.
  • Organizer: FASEB Summer Conferences-Signal Transduction in the Immune System
  • Place of Presentation: Snowmass Village, CO
  • Year and Date: 2011-06-23
• [Presentation] Immune cell activation under the microscope (2011)
  • Author(s): Saito, T.
  • Organizer: World Immune Regulation Meeting-V (WIRM) “Innate and Adaptive Immune Response and Role of Tissue in Immune Regulation"
  • Place of Presentation: Davos, Switzerland
  • Year and Date: 2011-03-25
• [Presentation] Spatio-temporal regulation of T cell activation (2010)
  • Author(s): Saito, T.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 2010-08-25
• [Presentation] Molecular dynamics for T cell activation and costimulation (2010)
  • Author(s): Saito, T.
  • Organizer: Keystone Symposia, Lymphocyte Activation and Gene Expression
  • Place of Presentation: Breckenridge, CO.
  • Year and Date: 2010-03-03
• [Presentation] Sensing self and non-self danger by ITAM-coupled innate receptor Mincle (2009)
  • Author(s): Saito, T., Yamasaki, S.
  • Organizer: FASEB Summer Research Conferences-Signal Transduction in the Immune System
  • Place of Presentation: Snowmass Village, CO.
  • Year and Date: 2009-06-23
• [Presentation] Dynamic regulation of TCRand costimulatory signals via microclusters (2008)
  • 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] CRTAM regulates retention of T cells within lymph node and delivery to effecter tissues (2008)
  • Author(s): Saito, T.
  • Organizer: Keystone Symposia/ Novel Modulators of Leukocyte Traffic
  • Place of Presentation: Keystone, CO. USA
  • Year and Date: 2008-01-16
• [Presentation] Dynamic regulation of T cell activation through TCR micloclusters (2007)
  • Author(s): Saito, T.
  • Organizer: 13^<th> International Congress of Immunology
  • Place of Presentation: Rio de Janeiro, Brazil
  • Year and Date: 2007-08-24
• [Presentation] TCR microclusters and co-stimulation for T cell activation (2007)
  • Author(s): Saito, T.
  • Organizer: EMBO Conference Series on “Signaling in the immune system” Lymphocyte antigen receptor and coreceptor signaling
  • Place of Presentation: Siena, Italy
  • Year and Date: 2007-05-26
• [Book] The immunological synapse, TCR microclusters, and T cell activation In: Chap. 5, Immunologial Synapse, Curr. Top. Microbiol. Immunol. T. Saito and F. D. Batista (eds.) 340 (2010)
  • Author(s): Yokosuka T, Saito T.
  • Total Pages: 81-107
  • Publisher: Springer-Verlag Berlin Heidelberg
• [Remarks]
  • URL: http://www.rcai.riken.go.jp/group/signaling/index.html
• [Patent(Industrial Property Rights)] T細胞受容体機能調節剤及びそのスクリーニング方法 (2009)
  • Inventor(s): 黒崎知博, 篠原久明
  • Industrial Property Rights Holder: 理化学研究所
  • Industrial Property Number: 特許,特願2009-053968
  • Filing Date: 2009-03-06
  • Overseas
• [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: 特許,特願2008-186570
  • Filing Date: 2008-07-17
  • Overseas
• [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: 特許,特願2008-285948
  • Filing Date: 2008-11-06
  • Overseas
• [Patent(Industrial Property Rights)] Ｔ細胞分化調節剤(および細胞表面タンパク質間の細胞外領域における相互作用の検出システム) (2007)
  • Inventor(s): 斉藤隆, 山崎晶
  • Industrial Property Rights Holder: 理化学研究所
  • Industrial Property Number: 特許,特願2007-539809
  • Filing Date: 2007-03-04
  • Overseas
• [Patent(Industrial Property Rights)] 肥満細胞の脱顆粒抑制剤 (2007)
  • Inventor(s): 黒崎知博, 馬場義裕
  • Industrial Property Rights Holder: 理化学研究所
  • Industrial Property Number: 特許,特願2007-273055
  • Filing Date: 2007-10-19
  • Overseas