Molecular mechanisms that set the stage for DC-T cell engagement

Klaas P J M van Gisbergen, Lutz C Paessens, Teunis B H Geijtenbeek, Yvette van Kooyk

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21 Citations (Scopus)


The unsurpassed capacity of dendritic cells (DC) to prime naive T cells is thought to depend on the formation of an immunological synapse. DC-SIGN, a C-type lectin exclusively expressed at the cell surface of DC, functions as an adhesion receptor facilitating T cell binding and priming through recognition of glycosylated ICAM-3 on naive T cells. Yet, DC-SIGN also mediates binding to pathogens such as HIV by recognizing glycosylated gp120. The scope of the present study was to investigate whether DC-SIGN upon recognition of its cellular ligand and pathogenic ligand affects DC synapse formation and activation/mobilization of other adhesion receptors such as LFA-1 to the cell contact site. Using a DC-SIGN deletion mutant, we show that DC-SIGN is a constitutively active receptor that mediates ligand binding independent of signaling through the cytoplasmic domain. Surprisingly, initial binding of gp120 to DC-SIGN did not result in increased adhesion levels of LFA-1 to its ligand ICAM-1 in both immature DC and Raji-DC-SIGN cells. However, ligand binding to DC-SIGN induced recruitment of LFA-1 to the adhesion site. Moreover, we could demonstrate that activation of LFA-1 results in DC-SIGN-LFA-1 co-clustering in the cell membrane. This triggers binding of ligands to LFA-1 that are shared with DC-SIGN, such as ICAM-3, but not of ligands that are not shared with DC-SIGN, such as ICAM-1. Thus, we propose that upon ligand binding DC-SIGN recruits LFA-1 to the contact site, resulting in the formation of DC-SIGN-LFA-1 co-clusters, in which the initial DC-SIGN-mediated interactions with ligand are transient and eventually shift to more stable LFA-1-dependent interactions.

Original languageEnglish
Pages (from-to)199-208
Number of pages10
JournalImmunology letters
Issue number2
Publication statusPublished - 2005


  • Antigens, CD/metabolism
  • Cell Adhesion Molecules
  • Cell Line, Tumor
  • Dendritic Cells/immunology
  • Humans
  • Intercellular Adhesion Molecule-1/metabolism
  • Lectins, C-Type/genetics
  • Ligands
  • Lymphocyte Function-Associated Antigen-1/metabolism
  • T-Lymphocytes/immunology

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