Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses

Cell. 2000 Mar 3;100(5):575-85. doi: 10.1016/s0092-8674(00)80693-5.

Abstract

Contact between dendritic cells (DC) and resting T cells is essential to initiate a primary immune response. Here, we demonstrate that ICAM-3 expressed by resting T cells is important in this first contact with DC. We discovered that instead of the common ICAM-3 receptors LFA-1 and alphaDbeta2, a novel DC-specific C-type lectin, DC-SIGN, binds ICAM-3 with high affinity. DC-SIGN, which is abundantly expressed by DC both in vitro and in vivo, mediates transient adhesion with T cells. Since antibodies against DC-SIGN inhibit DC-induced proliferation of resting T cells, our findings predict that DC-SIGN enables T cell receptor engagement by stabilization of the DC-T cell contact zone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigen Presentation*
  • Antigens / metabolism
  • Antigens, CD*
  • Antigens, Differentiation*
  • Calcium / physiology
  • Cell Adhesion
  • Cell Adhesion Molecules / immunology*
  • Cell Adhesion Molecules / isolation & purification
  • Cell Adhesion Molecules / metabolism
  • Cell Communication
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Intercellular Adhesion Molecule-1 / physiology
  • K562 Cells
  • Lectins / immunology
  • Lectins / physiology*
  • Lectins, C-Type*
  • Lymphocyte Activation / physiology*
  • Lymphocyte Function-Associated Antigen-1 / physiology
  • Mannans / pharmacology
  • Mannose / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Models, Immunological
  • Molecular Weight
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / physiology*
  • Receptors, HIV / isolation & purification
  • Recombinant Fusion Proteins / physiology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Transfection

Substances

  • Antibodies, Monoclonal
  • Antigens
  • Antigens, CD
  • Antigens, Differentiation
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • ICAM3 protein, human
  • Lectins
  • Lectins, C-Type
  • Lymphocyte Function-Associated Antigen-1
  • Mannans
  • Receptors, Cell Surface
  • Receptors, HIV
  • Recombinant Fusion Proteins
  • Intercellular Adhesion Molecule-1
  • Mannose
  • Calcium