The receptor for interleukin-6 (IL-6) is characterized by a ligand-binding glycoprotein 80 (gp80) transmembrane chain (IL-6R) which associates with a signal-transducer gp130 chain. We previously raised a series of monoclonal antibodies (mAb) recognizing different epitopes of the human IL-6R and interfering with the function of the receptor. One of them, M182, was able to diminish the proliferation of IL-6-dependent plasmacytoma cell lines although it was found unable to inhibit the binding of IL-6 to its receptor. Using an enzyme-linked immunosorbent assay for measuring the binding of IL-6-IL-6R to the gp130 chain, we showed that M182 was directed against a structure directly involved in the IL-6R/gp130 interaction. M182 was able to potentiate the inhibitor effect of anti-IL-6R mAB which interfere with the binding of IL-6, leading to complete inhibition of the proliferation of IL-6-dependent cell lines. M182 was also found to synergize with inhibitory anti-IL-6 mAb. Therefore this structure appears to be an important regulatory domain of the IL-6R and a valuable target For inhibiting IL-6 signalling.
Identification of a novel antigenic structure of the human receptor for interleukin-6 involved in the interaction with the glycoprotein 130 chain
Gaillard, J. P.; Liautard, J.; Mani, J. C.; Suarez, J. M. F.; Klein, B.; Brochier, J.
1996-09 / vol 89 / pages 135-141
growth; multiple-myeloma; affinity; gp130; antagonist; signal transducer; anti-interleukin-6 monoclonal-antibody; cell-lines; generation; human il-6 receptor