The dendritic cell cytoskeleton promotes T cell adhesion and activation by constraining ICAM-1 mobility

J Cell Biol. 2015 Feb 16;208(4):457-73. doi: 10.1083/jcb.201406120. Epub 2015 Feb 9.


Integrity of the dendritic cell (DC) actin cytoskeleton is essential for T cell priming, but the underlying mechanisms are poorly understood. We show that the DC F-actin network regulates the lateral mobility of intracellular cell adhesion molecule 1 (ICAM-1), but not MHCII. ICAM-1 mobility and clustering are regulated by maturation-induced changes in the expression and activation of moesin and α-actinin-1, which associate with actin filaments and the ICAM-1 cytoplasmic domain. Constrained ICAM-1 mobility is important for DC function, as DCs expressing a high-mobility ICAM-1 mutant lacking the cytoplasmic domain exhibit diminished antigen-dependent conjugate formation and T cell priming. These defects are associated with inefficient induction of leukocyte functional antigen 1 (LFA-1) affinity maturation, which is consistent with a model in which constrained ICAM-1 mobility opposes forces on LFA-1 exerted by the T cell cytoskeleton, whereas ICAM-1 clustering enhances valency and further promotes ligand-dependent LFA-1 activation. Our results reveal an important new mechanism through which the DC cytoskeleton regulates receptor activation at the immunological synapse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actinin / genetics
  • Actinin / metabolism
  • Amino Acid Sequence
  • Animals
  • B7-2 Antigen / biosynthesis
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD40 Antigens / biosynthesis
  • Cell Adhesion / genetics
  • Cells, Cultured
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology*
  • Enzyme Activation / genetics
  • Genes, MHC Class II / genetics
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Mutation
  • Protein Structure, Tertiary / genetics
  • RNA Interference
  • RNA, Small Interfering
  • Sequence Alignment


  • Actn1 protein, mouse
  • B7-2 Antigen
  • CD40 Antigens
  • Cd86 protein, mouse
  • Icam1 protein, mouse
  • Lymphocyte Function-Associated Antigen-1
  • Microfilament Proteins
  • RNA, Small Interfering
  • Actinin
  • Intercellular Adhesion Molecule-1
  • moesin