Identification of different binding sites in the dendritic cell-specific receptor DC-SIGN for intercellular adhesion molecule 3 and HIV-1

Teunis B H Geijtenbeek, Gerard C F van Duijnhoven, Sandra J van Vliet, Elmar Krieger, Gert Vriend, Carl G Figdor, Yvette van Kooyk

Research output: Contribution to journalArticleAcademicpeer-review

167 Citations (Scopus)


The novel dendritic cell (DC)-specific human immunodeficiency virus type 1 (HIV-1) receptor DC-SIGN plays a key role in the dissemination of HIV-1 by DC. DC-SIGN is thought to capture HIV-1 at mucosal sites of entry, facilitating transport to lymphoid tissues, where DC-SIGN efficiently transmits HIV-1 to T cells. DC-SIGN is also important in the initiation of immune responses by regulating DC-T cell interactions through intercellular adhesion molecule 3 (ICAM-3). We have characterized the mechanism of ligand binding by DC-SIGN and identified the crucial amino acids involved in this process. Strikingly, the HIV-1 gp120 binding site in DC-SIGN is different from that of ICAM-3, consistent with the observation that glycosylation of gp120, in contrast to ICAM-3, is not crucial to the interaction with DC-SIGN. A specific mutation in DC-SIGN abrogated ICAM-3 binding, whereas the HIV-1 gp120 interaction was unaffected. This DC-SIGN mutant captured HIV-1 and infected T cells in trans as efficiently as wild-type DC-SIGN, demonstrating that ICAM-3 binding is not necessary for HIV-1 transmission. This study provides a basis for the design of drugs that inhibit or alter interactions of DC-SIGN with gp120 but not with ICAM-3 or vice versa and that have a therapeutic value in immunological diseases and/or HIV-1 infections.

Original languageEnglish
Pages (from-to)11314-20
Number of pages7
JournalJournal of Biological Chemistry
Issue number13
Publication statusPublished - 29 Mar 2002


  • Amino Acid Sequence
  • Antigens, CD
  • Antigens, Differentiation
  • Binding Sites
  • Cell Adhesion Molecules/metabolism
  • Glycosylation
  • HIV-1/metabolism
  • Humans
  • Lectins, C-Type
  • Lectins/chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Receptors, Cell Surface/chemistry
  • Sequence Homology, Amino Acid

Cite this