RESEARCH ARTICLE


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
1 Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada
2 Current address: Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 West Markham, Slot 634, Little Rock, AR 72205, USA
3 Current address: Genome Science Centre, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada
4 Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, V6T 2B5, Canada


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© 2008 Mace et al.;

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.

* Address correspondence to this author at the Terry Fox Laboratory, BC Cancer Agency, 675 W. 10th Ave., Vancouver, B.C., V5Z 1L3, Canada; Tel: (604) 675-8131; Fax: (604) 877-0712; E-mail: ftakei@bccrc.ca


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.

Keywords: LFA-1, T lymphocytes, Adhesion Molecules, ICAM-1, Cytotoxic T Cell, Actin, Talin.