Epitope mapping on the dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) pathogen-attachment factor

Mol Immunol. 2010 Jan;47(4):840-8. doi: 10.1016/j.molimm.2009.09.036. Epub 2009 Oct 30.

Abstract

DC-SIGN (dendritic cell-specific ICAM-3-grabbing non-integrin) is a myeloid pathogen-attachment factor C-type lectin which recognizes mannose- and fucose-containing oligosaccharide ligands on clinically relevant pathogens. Intracellular signaling initiated upon ligand engagement of DC-SIGN interferes with TLR-initiated signals, and modulates the T cell activating and polarizing ability of antigen-presenting cells. The C-terminal carbohydrate-recognition domain (CRD) of DC-SIGN is preceded by a neck domain composed of eight 23-residue repeats which mediate molecule multimerization, and whose polymorphism correlates with altered susceptibility to SARS and HIV infection. Naturally occurring isoforms and chimaeric molecules, in combination with established recognition properties, were used to define seven structural and functional epitopes on DC-SIGN. Three epitopes mapped to the CRD, one of which is multimerization-dependent and only exposed on DC-SIGN monomers. Epitopes within the neck domain were conformation-independent and unaltered upon molecule multimerization, but were differentially affected by neck domain truncations. Although neck-specific antibodies exhibited lower function-blocking ability, they were more efficient at inducing molecule internalization. Moreover, crosslinking of the different epitopes resulted in distinct levels of microclustering on the cell surface. The identification of independent epitopes on the DC-SIGN molecule might facilitate the design of reagents that modulate the T cell activating and polarizing ability of DC-SIGN-expressing cells without preventing its antigen- and pathogen-recognition capacities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Blocking / immunology
  • Antibodies, Monoclonal / immunology
  • Antibody Specificity / immunology
  • Cell Adhesion Molecules / chemistry*
  • Cell Adhesion Molecules / immunology*
  • Cell Line
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Endocytosis / immunology
  • Epitope Mapping*
  • Fluorescent Antibody Technique
  • Humans
  • Lectins, C-Type / chemistry*
  • Lectins, C-Type / immunology*
  • Monocytes / cytology
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / immunology*

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface