Epitope peptides from interleukin-6 receptor which inhibit the growth of human myeloma cells.

Abstract

A panel of monoclonal antibodies against the soluble IL-6 receptor was used to search for linear epitopes by a Pepscan analysis. Two such epitopes were found and the corresponding peptides were synthesized chemically. The peptides were active to inhibit the IL-6 dependent growth of human multiple myeloma cell line and the effect of IL-6 on growth of murine hybridoma cells. The epitope-defined, antagonist peptides reduced the transduction of the IL-6 signal which activates binding of Stat transcription factors to specific enhancers, but did not affect IL-6 binding. These effects were not seen with several other peptides from the IL-6 receptor sequence. A computer three-dimensional model of the IL-6 receptor complex was built and indicates that the antagonist peptides define one of the two possible sites of interaction between the domain-II of the IL-6 receptor molecule and that of the gp130 molecule within the hexameric receptor assembly.