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.