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Blood, 1 January 2007, Vol. 109, No. 1, pp. 168-175.
Prepublished online as a Blood First Edition Paper on September 14, 2006; DOI 10.1182/blood-2005-12-020164.
Previous Article | Next Article 
Submitted December 13, 2005
Accepted August 15, 2006
Actin cloud induced by LFA-1-mediated outside-in signals
lowers the threshold for T cell activation
Jun-ichiro Suzuki, Sho Yamasaki, Jennifer Wu, Gary A. Koretzky, and Takashi Saito*
Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Japan
RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan
University of Pennsylvania School of Medicine, Abramson Family Cancer Research Institute, PA, USA
* Corresponding author; email: saito{at}rcai.riken.jp.
The dynamic rearrangement of the actin cytoskeleton plays critical roles in TCR signaling and immunological synapse (IS) formation in T cells. Following actin rearrangement in T cells upon TCR stimulation, we found a unique ring-shaped reorganization of actin called "actin cloud," which was specifically induced by outside-in signals through LFA-1 engagement. Under T cell-APC interaction, the actin cloud is generated in the absence of antigen and localized at the center of the T cell-APC interface, where it accumulates LFA-1 and tyrosine-phosphorylated proteins. The LFA-1-induced actin cloud formation involves ADAP phosphorylation, LFA-1/ADAP assembly and JNK activation, and occurs independent of TCR and its proximal signaling. The formation of the actin cloud lowers the threshold for subsequent T cell activation. Thus, the actin cloud induced by LFA-1 engagement may serve as a possible platform for LFA-1-mediated co-stimulatory function for T cell activation.

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