title: Micro-adhesion rings surrounding TCR microclusters are essential for T cell activation.
abstract: The immunological synapse (IS) formed at the interface between T cells and antigen-presenting cells represents a hallmark of initiation of acquired immunity. T cell activation is initiated at T cell receptor (TCR) microclusters (MCs), in which TCRs and signaling molecules assemble at the interface before IS formation. We found that each TCR-MC was transiently bordered by a ring structure made of integrin and focal adhesion molecules in the early phase of activation, which is similar in structure to the IS in microscale. The micro-adhesion ring is composed of LFA-1, focal adhesion molecules paxillin and Pyk2, and myosin II (MyoII) and is supported by F-actin core and MyoII activity through LFA-1 outside-in signals. The formation of the micro-adhesion ring was transient but especially sustained upon weak TCR stimulation to recruit linker for activation of T cells (LAT) and SLP76. Perturbation of the micro-adhesion ring induced impairment of TCR-MC development and resulted in impaired cellular signaling and cell functions. Thus, the synapse-like structure composed of the core TCR-MC and surrounding micro-adhesion ring is a critical structure for initial T cell activation through integrin outside-in signals.
authors.affiliation: Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan takashi.saito@riken.jp akiko.tane@riken.jp.
authors.forename: Akiko
authors.identifier: 0000-0001-8519-266X
authors.initials: A
authors.lastname: Hashimoto-Tane
authors.affiliation: Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Machie
authors.initials: M
authors.lastname: Sakuma
authors.affiliation: Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan Laboratory for Cell Signaling, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.identifier: 0000-0002-4365-080X
authors.initials: H
authors.lastname: Ike
authors.affiliation: Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yokosuka
authors.affiliation: Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Yayoi
authors.identifier: 0000-0002-4612-4602
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan.
authors.forename: Osamu
authors.identifier: 0000-0002-3328-9571
authors.initials: O
authors.lastname: Ohara
authors.affiliation: Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan Laboratory for Cell Signaling, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan takashi.saito@riken.jp akiko.tane@riken.jp.
authors.forename: Takashi
authors.identifier: 0000-0001-9495-3547
authors.initials: T
authors.lastname: Saito
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D000818:Animals; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D051419:Paxillin / Q000235:genetics / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491734:Lat protein, mouse; D016169:Lymphocyte Function-Associated Antigen-1; D008565:Membrane Proteins; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse