title: Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48.
abstract: 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.
authors.affiliation: Department of Immunobiology, Immunex Corporation, Seattle, USA. mkubin@immunex.com
authors.forename: M Z
authors.initials: MZ
authors.lastname: Kubin
authors.forename: D L
authors.initials: DL
authors.lastname: Parshley
authors.forename: W
authors.initials: W
authors.lastname: Din
authors.forename: J Y
authors.initials: JY
authors.lastname: Waugh
authors.forename: T
authors.initials: T
authors.lastname: Davis-Smith
authors.forename: C A
authors.initials: CA
authors.lastname: Smith
authors.forename: B M
authors.initials: BM
authors.lastname: Macduff
authors.forename: R J
authors.initials: RJ
authors.lastname: Armitage
authors.forename: W
authors.initials: W
authors.lastname: Chin
authors.forename: L
authors.initials: L
authors.lastname: Cassiano
authors.forename: L
authors.initials: L
authors.lastname: Borges
authors.forename: M
authors.initials: M
authors.lastname: Petersen
authors.forename: G
authors.initials: G
authors.lastname: Trinchieri
authors.forename: R G
authors.initials: RG
authors.lastname: Goodwin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology; D000071178:CD48 Antigen; D002455:Cell Division; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D019169:Jurkat Cells; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000378:metabolism*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012333:RNA, Messenger; D011971:Receptors, Immunologic / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family; D014443:Tyrosine / Q000378:metabolism; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C084093:CD244 protein, human; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C490007:Cd244a protein, mouse; C000604066:Cd48 protein, mouse; D016207:Cytokines; D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D000071176:Signaling Lymphocytic Activation Molecule Family; D014443:Tyrosine; D007371:Interferon-gamma