|
 |
|
|
| Subject Categories: Cell & Tissue Architecture | Immunology |
|
| The EMBO Journal
(2008) 27, 62–75, doi:10.1038/sj.emboj.7601959 Published online 13 December 2007 |
|
Intermediate-affinity LFA-1 binds  -actinin-1 to control migration at the leading edge of the T cellEMBO Open |
|
|
| Paula Stanley1, 3, Andrew Smith1, 3, 4, Alison McDowall1, Alastair Nicol2, Daniel Zicha2 and Nancy Hogg1 |
|
|
1 Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, London, UK 2 Light Microscopy Laboratory, Cancer Research UK London Research Institute, London, UK To whom correspondence should be addressed Nancy Hogg, Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. Tel.: +44 207 269 3255; Fax: +44 207 269 3093; E-mail: nancy.hogg@cancer.org.uk 3 These authors contributed equally to this work 4 Present address: Department of Medicine, University College London, London WC1E 6JJ, UK Received 8 February 2007; Accepted 20 November 2007; Published online 13 December 2007. |
|
|
|
| Abstract |
|
| T lymphocytes use LFA-1 to migrate into lymph nodes and inflammatory sites. To investigate the mechanisms regulating this migration, we utilize mAbs selective for conformational epitopes as probes for active LFA-1. Expression of the KIM127 epitope, but not the 24 epitope, defines the extended conformation of LFA-1, which has intermediate affinity for ligand ICAM-1. A key finding is that KIM127-positive LFA-1 forms new adhesions at the T lymphocyte leading edge. This LFA-1 links to the cytoskeleton through -actinin-1 and disruption at the level of integrin or actin results in loss of cell spreading and migratory speed due to a failure of attachment at the leading edge. The KIM127 pattern contrasts with high-affinity LFA-1 that expresses both 24 and KIM127 epitopes, is restricted to the mid-cell focal zone and controls ICAM-1 attachment. Identification of distinctive roles for intermediate- and high-affinity LFA-1 in T lymphocyte migration provides a biological function for two active conformations of this integrin for the first time. |
|
| Keywords: -Actinin-1, integrin, LFA-1, migration, T lymphocyte |
|
|
|
Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSCrawling and INTEGRating apical cues Nature Immunology News and Views (01 Apr 2004) Integrin activation under flow: a local affair Nature Immunology News and Views (01 May 2005) RESEARCHOrigins of HTLV-1 in South America (letter 2) Nature Medicine Letters to Editor (01 Mar 2000) Increased CCR4 Expression in Cutaneous T Cell Lymphoma Journal of Investigative Dermatology Original Article |
|
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Next article |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
 | Rights and permissions |
| |
 | Reprints |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |