Identification of a novel antigenic structure of the human receptor for interleukin‐6 involved in the interaction with the glycoprotein 130 chain

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Abstract
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.