PRODUCTION AND CHARACTERIZATION OF MONOCLONAL-ANTIBODIES AGAINST THE LEUKEMIA INHIBITORY FACTOR LOW-AFFINITY RECEPTOR, GP190

Leukemia inhibitory factor (LIF), oncostatin-M (OSM), ciliary neurotro phic 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 c hain, with the IL6 and IL11 receptors. Because IL6 and gp130 were the first members to be discovered, most of the available reagents are dir ected at them. In this respect, monoclonal antibodies have played a ma jor role in elucidating these receptor/ligand interactions and explori ng the pathophysiological aspects of their biology. So far, no such re agents have been described for the gp190. We now report the production and characterization of 16 monoclonal antibodies directed against hum an gp190. They were obtained using recombinant chimeric or truncated p roteins produced in a eukaryotic CHO cell line. One was able to block the biological activity of LIF. Because gp190 comprises two hematopoie tin binding domains, crude epitope mapping was possible using the same reagents. While more of these antibodies are required, the present se t validate the technological approach used for their preparation and s hould improve our understanding of this class of cytokines. (C) 1997 E lsevier Science B.V.