EPITOPE PEPTIDES FROM INTERLEUKIN-6 RECEPTOR WHICH INHIBIT THE GROWTHOF HUMAN MYELOMA CELLS

A panel of monoclonal antibodies against the soluble IL-6 receptor was used to search for linear epitopes by a Pepscan analysis, Two such ep itopes were found and the corresponding peptides were synthesized chem ically. 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 o f murine hybridoma cells. The epitope-defined, antagonist peptides red uced the transduction of the IL-6 signal which activates binding of St at transcription factors to specific enhancers, but did not affect IL- 6 binding, These effects were not seen with several other peptides fro m the IL-6 receptor sequence. A computer three-dimensional model of th e IL-6 receptor complex was built and indicates that the antagonist pe ptides define one of the two possible sites of interaction between the domain-II of the IL-6 receptor molecule and that of the gp130 molecul e within the hexameric receptor assembly.