Low-affinity LFA-1/ICAM-3 interactions augment LFA-1/ICAM-1-mediated T cell adhesion and signaling by redistribution of LFA-1

D A Bleijs, M E Binnerts, S J van Vliet, C G Figdor, Y van Kooyk

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Although ICAM-3 is implicated in both adhesion and signal transduction events of leukocytes, its low affinity for LFA-1 compared to other ligands of LFA-1 has puzzled many investigators. Here we investigated the role of ICAM-3 in supporting LFA-1-mediated ICAM-1 binding and subsequently cell signaling. We observed that although ICAM-3 binds poorly to LFA-1 expressed on resting T cells, it specifically facilitates and increases LFA-1-mediated adhesion to the high affinity ligand of LFA-1, ICAM-1. We demonstrate that low-affinity binding of LFA-1 to ICAM-3 together with ICAM-1 alters the cell surface distribution of LFA-1 dramatically, inducing large clusters of LFA-1 that facilitate ICAM-1 binding after LFA-1 activation. We found that LFA-1-mediated ICAM-1 cell-cell interactions such as T cell proliferation greatly depend on low affinity LFA-1/ICAM-3 interactions that enhance stable LFA-1/ICAM-1 cell-cell contact. Taken together, these data demonstrate that low affinity LFA-1 binding to ICAM-3 regulates strong LFA-1/ICAM-1-mediated adhesion by driving LFA-1 into clusters to facilitate cell-cell interactions that take place in the immune system.

Original languageEnglish
Pages (from-to)391-400
Number of pages10
JournalJournal of Cell Science
Volume113 ( Pt 3)
Publication statusPublished - Feb 2000


  • Antigens, CD
  • Antigens, Differentiation
  • Cell Adhesion
  • Cell Adhesion Molecules/pharmacology
  • Cell Division
  • Cells, Cultured
  • Humans
  • K562 Cells
  • Lymphocyte Activation
  • Lymphocyte Function-Associated Antigen-1/physiology
  • Neoplasm Proteins/physiology
  • Recombinant Proteins/pharmacology
  • Signal Transduction
  • T-Lymphocytes/cytology

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