Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48.
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.
Kubin
M Z
MZ
Department of Immunobiology, Immunex Corporation, Seattle, USA. mkubin@immunex.com
Parshley
D L
DL
Din
W
W
Waugh
J Y
JY
Davis-Smith
T
T
Smith
C A
CA
Macduff
B M
BM
Armitage
R J
RJ
Chin
W
W
Cassiano
L
L
Borges
L
L
Petersen
M
M
Trinchieri
G
G
Goodwin
R G
RG
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
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