Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I-restricted T-cell-associated molecule

J Biol Chem. 2005 Jun 10;280(23):21955-64. doi: 10.1074/jbc.M502095200. Epub 2005 Mar 21.

Abstract

Dendritic cells (DCs) are a phenotypically and functionally heterogenous population of leukocytes with distinct subsets serving a different set of specialized immune functions. Here we applied an in vitro whole cell panning approach using antibody phage display technology to identify cell-surface epitopes specifically expressed on human blood BDCA3(+) DCs. A single-chain antibody fragment (anti-1F12 scFv) was isolated that recognizes a conserved surface antigen expressed on both human BDCA3(+) DCs and mouse CD8alpha(+) DCs. We demonstrate that anti-1F12 scFv binds Nectin-like protein 2 (Necl2, Tslc1, SynCaM, SgIGSF, or Igsf4), an adhesion molecule involved in tumor suppression, synapse formation, and spermatogenesis. Thus, Necl2 defines a specialized subset of DCs in both mouse and human. We further show that Necl2 binds Class-I-restricted T-cell-associated molecule (CRTAM), a receptor primarily expressed on activated cytotoxic lymphocytes. When present on antigen presenting cells, Necl2 regulates IL-22 expression by activated CD8(+) T-cells. We propose that Necl2/CRTAM molecular pair could regulate a large panel of cell/cell interactions both within and outside of the immune system.

MeSH terms

  • Animals
  • Blotting, Western
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Adhesion
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Cell Aggregation
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Separation
  • Coculture Techniques
  • Dendritic Cells / cytology*
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Flow Cytometry
  • Humans
  • Immune System / physiology
  • Immunoblotting
  • Immunoglobulins / metabolism*
  • Immunoglobulins / physiology*
  • Immunoprecipitation
  • Interleukin-22
  • Interleukins / biosynthesis
  • Lentivirus / genetics
  • Leukocytes / metabolism
  • Ligands
  • Lymphocytes / cytology
  • Mass Spectrometry
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Octoxynol / pharmacology
  • Peptide Library
  • Phenotype
  • Polymerase Chain Reaction
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Spleen / metabolism
  • T-Lymphocytes / metabolism*

Substances

  • Cadm1 protein, mouse
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Immunoglobulins
  • Interleukins
  • Ligands
  • Membrane Proteins
  • Peptide Library
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • class-I restricted T cell-associated molecule
  • Octoxynol