Provided is an antibody muM4TS.22 that specific for the platelet-derived growth factor receptor β. muM4TS.22 does not bind to deletion proteins containing only the first through second domains of PDGF-R β, but does bind to protein D1-3 containing the third domain, showing that the binding epitope is in the third domain. muM4TS.22 effectively inhibited the stimulation of proliferation by PDGF BB, showing the ability of these antibodies to neutralize the biological activity of PDGF BB.
Figure 1 M4TS.22 inhibited both PDGF BB binding to PDGFRb and PDGF BB-mediated proliferation. M4TS.11 and M4TS.22 were indistinguishable in their ability to inhibit PDGF BB-mediated proliferation.
A, effect of anti-PDGFRb antibodies on 125I-labeled PDGF BB binding to PDGFRb 1 cells. CHO C4 cells expressing the human PDGFRb were preincubated with 5 m g of the indicated antibody. Addition of 100 ng of unlabeled PDGF BB served to indicate the level of nonspecific 125I-labeled PDGF BB binding. B, effect of anti-PDGFRb antibodies on PDGF BB-mediated proliferation. CHO C4 cells were preincubated with various concentrations of M4TS.11 (●), M4TS.15 (▲), or M4TS.22 (■) for 2 h, after which PDGF BB was added.
Shulman, T., Sauer, F. G., Jackman, R. M., Chang, C. N., & Landolfi, N. F. (1997). An antibody reactive with domain 4 of the platelet-derived growth factor β receptor allows BB binding while inhibiting proliferation by impairing receptor dimerization. Journal of Biological Chemistry, 272(28), 17400-17404.
Figure 2 Binding of the M4TS antibodies to PDGFRb domain deletion mutants. Reactivity of M4TS.11, M4TS.15, and M4TS.22 with various PDGFRb deletion mutants was determined by ELISA.
This analysis revealed that M4TS.22 was dependent on the presence of extracellular domain 3.
Shulman, T., Sauer, F. G., Jackman, R. M., Chang, C. N., & Landolfi, N. F. (1997). An antibody reactive with domain 4 of the platelet-derived growth factor β receptor allows BB binding while inhibiting proliferation by impairing receptor dimerization. Journal of Biological Chemistry, 272(28), 17400-17404.
Figure 3 Effect of anti-PDGFRb antibodies on PDGF BB-mediated proliferation of baboon and rabbit cells.
It demonstrates that preincubation with either M4TS.11 or M4TS.22 significantly decreased PDGF BB-mediated proliferation of the baboon SMC.
Shulman, T., Sauer, F. G., Jackman, R. M., Chang, C. N., & Landolfi, N. F. (1997). An antibody reactive with domain 4 of the platelet-derived growth factor β receptor allows BB binding while inhibiting proliferation by impairing receptor dimerization. Journal of Biological Chemistry, 272(28), 17400-17404.
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