LFA-1 Binding to Ligand Induces Talin-Mediated Reorganization of the Actin Cytoskeleton in Cytotoxic T Cells

ABSTRACT

LFA-1 mediates binding of cytotoxic T lymphocytes (CTLs) to target cells. However, the role of LFA-1 in CTLs beyond its cell adhesion function has been unclear. We have investigated the role of LFA-1 in reorganization of the actin cytoskeleton, an essential step in cell-mediated cytotoxicity. Binding of LFA-1 to ICAM-1, but not anti-LFA-1 cross-linking, induces the accumulation of talin, WASP and actin in an antigen independent manner. Antibody crosslinking of LFA-1 on CTLs induces its capping, but talin, actin and WASP remain evenly distributed, indicating that they do not constitutively associate with LFA-1 in CTLs. These results show that ligand binding, but not simple clustering of LFA-1, induces its association with talin and provides stimulatory signals in CTLs leading to the reorganization of the actin cytoskeleton independently of TCR-mediated signaling.

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