Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 213, Issue 8, Pages 1609-1625Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20151088
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Funding
- Japan Society for the Promotion of Science [JP24229004, JP10415226]
- Takeda Science Foundation [F1206042]
- Novartis Foundation
- Hayashi Memorial Foundation for Female Natural Scientists
- Grants-in-Aid for Scientific Research [16H05230] Funding Source: KAKEN
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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.
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