Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines

Nat Immunol. 2005 May;6(5):497-506. doi: 10.1038/ni1194. Epub 2005 Apr 17.


It is widely believed that rolling lymphocytes require successive chemokine-induced signaling for lymphocyte function-associated antigen 1 (LFA-1) to achieve a threshold avidity that will mediate lymphocyte arrest. Using an in vivo model of lymphocyte arrest, we show here that LFA-1-mediated arrest of lymphocytes rolling on high endothelial venules bearing LFA-1 ligands and chemokines was abrupt. In vitro flow chamber models showed that endothelium-presented but not soluble chemokines triggered instantaneous extension of bent LFA-1 in the absence of LFA-1 ligand engagement. To support lymphocyte adhesion, this extended LFA-1 conformation required immediate activation by its ligand, intercellular adhesion molecule 1. These data show that chemokine-triggered lymphocyte adhesiveness involves a previously unrecognized extension step that primes LFA-1 for ligand binding and firm adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Cell Adhesion
  • Cells, Cultured
  • Chemokines / metabolism*
  • Chemokines / pharmacology
  • Cytoskeleton / metabolism
  • Endothelium / metabolism*
  • Epitopes / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymphocyte Function-Associated Antigen-1 / chemistry*
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Lymphocytes / cytology*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Protein Conformation / drug effects
  • Protein Subunits / immunology
  • Protein Subunits / metabolism
  • Solubility
  • Talin / metabolism


  • Chemokines
  • Epitopes
  • Lymphocyte Function-Associated Antigen-1
  • Protein Subunits
  • Talin
  • Intercellular Adhesion Molecule-1