Production and characterization of monoclonal antibodies against the leukemia inhibitory factor low affinity receptor, gp190.
Leukemia inhibitory factor (LIF), oncostatin-M (OSM), ciliary neurotrophic factor (CNTF) and cardiotrophin-1 (CT1) act through transmembrane receptors which share the gp190 glycoprotein chain. The understanding of its involvement in the biology of these cytokines is of importance since these systems have recently been shown to participate in major inflammatory and neoplastic processes such as myelomatosis (Rose-John, S., Heinrich, P.C., 1994. Soluble receptors for cytokines and growth factors: generation and biological function. Biochem. J. 300, 281). In addition, this family of receptors also shares the gp130 transducing chain, with the IL6 and IL11 receptors. Because IL6 and gp130 were the first members to be discovered, most of the available reagents are directed at them. In this respect, monoclonal antibodies have played a major role in elucidating these receptor/ligand interactions and exploring the pathophysiological aspects of their biology. So far, no such reagents have been described for the gp190. We now report the production and characterization of 16 monoclonal antibodies directed against human gp190. They were obtained using recombinant chimeric or truncated proteins produced in a eukaryotic CHO cell line. One was able to block the biological activity of LIF. Because gp190 comprises two hematopoietin binding domains, crude epitope mapping was possible using the same reagents. While more of these antibodies are required, the present set validate the technological approach used for their preparation and should improve our understanding of this class of cytokines.
Pitard
V
V
CNRS-UMR 5540, Université de Bordeaux 2, France.
Taupin
J L
JL
Miossec
V
V
Blanchard
F
F
Cransac
M
M
Jollet
I
I
Vernallis
A
A
Hudson
K
K
Godard
A
A
Jacques
Y
Y
Moreau
J F
JF
D000818:Animals; D019138:Antibodies, Blocking / Q000096:biosynthesis / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000494:pharmacology; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D007114:Immunization; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D053606:Receptors, OSM-LIF; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D017931:DNA Primers; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D011993:Recombinant Fusion Proteins