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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.
IMMUNOBIOLOGY The actin cloud induced by LFA-1mediated outside-in signals lowers the threshold for T-cell activation1 Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Japan; 2 Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; 3 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Abramson Family Cancer Research Institute, Philadelphia
The dynamic rearrangement of the actin cytoskeleton plays critical roles in T-cell receptor (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 the "actin cloud," which was specifically induced by outside-in signals through lymphocyte functionassociated antigen-1 (LFA-1) engagement. In T-cellantigen-presenting cell (APC) interactions, the actin cloud is generated in the absence of antigen and localized at the center of the T-cellAPC interface, where it accumulates LFA-1 and tyrosine-phosphorylated proteins. The LFA-1induced actin cloud formation involves ADAP (adhesion- and degranulation-promoting adaptor protein) phosphorylation, LFA-1/ADAP assembly, and c-Jun N-terminal kinase (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-1mediated costimulatory function for T-cell activation.
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