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7070695 
Journal Article 
Micro-adhesion rings surrounding TCR microclusters are essential for T cell activation 
Hashimoto-Tane, A; Sakuma, M; Ike, H; Yokosuka, T; Kimura, Y; Ohara, O; Saito, T; , 
2016 
Yes 
Journal of Experimental Medicine
ISSN: 0022-1007
EISSN: 1540-9538 
ROCKEFELLER UNIV PRESS 
NEW YORK 
1609-1625 
English 
27354546 
WOS:000380851200016 
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.