HIGH-AFFINITY INTERLEUKIN-6 RECEPTOR IS A HEXAMERIC COMPLEX CONSISTING OF 2 MOLECULES EACH OF INTERLEUKIN-6, INTERLEUKIN-6 RECEPTOR, AND GP-130

The high affinity human interleukin-6 (IL-6) receptor complex consists of IL-6 and two membrane-associated receptor components, the IL-6 rec eptor (alpha-subunit) and the high affinity converter and signal trans ducing molecule, gp-130 (beta-subunit). Recombinant IL-6 and the extra cellular (''soluble'') components of the IL-6 receptor (sIL-6R) and gp -130 (sgp-130) have been prepared in order to investigate the stoichio metry and binding of these components in the low affinity (IL-6.sIL-6R ) and high affinity (IL-6 sIL-6R.sgp-130) IL-6 receptor complexes. Usi ng a combination of size-exclusion chromatography and analytical ultra centrifugation analysis, in the low affinity receptor complex, IL-6 wa s shown to bind sIL-6R in a stoichiometric ratio of 1:1, whereas the h igh affinity ternary complex is hexameric consisting of two molecules each of IL-6, sIL-6R, and sgp-130. This is the first direct demonstrat ion of a higher order arrangement for receptor cytokine interactions t hat exhibit both high and low affinity complexes.