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Neutralizing and nonneutralizing monoclonal antibodies to the human
granulocyte-macrophage colony-stimulating factor receptor alpha-chain
NA Nicola, K Wycherley, AW Boyd, JE Layton, D Cary and D Metcalf
Walter and Eliza Hall Institute of Medical Research, Ludwig Institute for
Cancer Research-Melbourne Tumour Biology Branch, Parkville, Australia.
A panel of monoclonal antibodies was raised against the low-affinity human
granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor
alpha-chain expressed as recombinant protein on murine FDC-P1 cells. All
the selected antibodies were of the IgG2A isotype and bound to protein A.
They each recognized both native and recombinant receptors by indirect
surface immunofluorescence and by immunoprecipitation. Several of the
antibodies also recognized presumably denatured receptors as detected by
immunoblotting of sodium dodecyl sulfate-polyacrylamide gel
electrophoresis. Three different epitopes on the extracellular domain of
the GM-CSF receptor alpha-chain were defined by these antibodies, and two
of the epitopes did not appear to be involved in binding hGM-CSF or in
interactions with the beta-chain of the GM-CSF receptor that are required
for high-affinity binding of GM-CSF. On the other hand, the epitope
recognized by antibody 2B7-17-A appeared to be critically involved in the
binding of GM-CSF because this antibody completely abrogated both high- and
low- affinity binding of GM-CSF to native and recombinant receptors.
Antibody 2B7-17-A had a relatively high affinity for the GM-CSF receptor
alpha-chain (kd = 3 nmol/L) and slow dissociation kinetics (kd = 0.002
min-1). These properties made the 2B7-17-A antibody a potent inhibitor of
hGM-CSF biologic action in several different bioassays, with a half-maximal
inhibitory dose of about 6 nmol/L (1 microgram/mL). This antibody could
prove useful in alleviating any pathologic states mediated by excess GM-CSF
levels and in defining the domains of the GM- CSF receptor required for
ligand binding.
Volume 82,
Issue 6,
pp. 1724-1731,
09/15/1993
Copyright © 1993 by The American Society of Hematology
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