Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48

Eur J Immunol. 1999 Nov;29(11):3466-77. doi: 10.1002/(SICI)1521-4141(199911)29:11<3466::AID-IMMU3466>3.0.CO;2-9.


Using the monoclonal antibody C1.7, which recognizes a signaling, membrane-bound molecule on human NK and a proportion of CD8(+) T cells, we cloned a novel molecule we refer to as NK cell activation-inducing ligand (NAIL). It is a 365-amino acid protein that belongs to the immunoglobulin-like superfamily with closest homology to murine 2B4, and human CD84 and CD48. Using a soluble NAIL-Fc fusion protein, we determined the counterstructure for NAIL, CD48, which it binds with high affinity. Stimulation of human B cells with recombinant NAIL in the presence of a suboptimal concentration of human CD40 ligand or IL-4 resulted in increased proliferation. Treatment of human dendritic cells with soluble NAIL-leucine zipper protein resulted in an increased release of IL-12 and TNF-alpha. Using recombinant CD48 protein, we demonstrated the ability of this molecule to increase NK cell cytotoxicity and induce IFN-gamma production. We also showed that 2B4 binds to mouse CD48, suggesting that interaction of these receptors may play a similar role in both species. Taken together these results indicate that the NAIL-CD48 interaction may be an important mechanism regulating a variety of immune responses.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / metabolism*
  • B-Lymphocytes / cytology
  • CD48 Antigen
  • Cell Division
  • Cloning, Molecular
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic
  • Humans
  • Immunoglobulin Fc Fragments / metabolism
  • Interferon-gamma / biosynthesis
  • Jurkat Cells
  • K562 Cells
  • Killer Cells, Natural / metabolism*
  • Ligands
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • RNA, Messenger
  • Receptors, Immunologic / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Signaling Lymphocytic Activation Molecule Family
  • Tyrosine / metabolism
  • U937 Cells
  • Up-Regulation


  • Antigens, CD
  • CD244 protein, human
  • CD48 Antigen
  • CD48 protein, human
  • Cd244a protein, mouse
  • Cd48 protein, mouse
  • Cytokines
  • Immunoglobulin Fc Fragments
  • Ligands
  • Membrane Glycoproteins
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • Signaling Lymphocytic Activation Molecule Family
  • Tyrosine
  • Interferon-gamma