LFA-1 Binding to Ligand Induces Talin-Mediated Reorganization of the Actin Cytoskeleton in Cytotoxic T Cells
Emily M. Macea, Matthew A. MacLeoda, Muhammad Reza Marwalia, b, Lisa Dreoliniaa, c, Fumio Takeia, d
Identifiers and Pagination:Year: 2008
First Page: 51
Last Page: 61
Publisher Id: TOIJ-1-51
Article History:Received Date: 24/07/2008
Revision Received Date: 20/09/2008
Acceptance Date: 14/11/2008
Electronic publication date: 5/12/2008
Collection year: 2008
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.