The relationship between the binding ability and the rate of activation of the complement component C1.

The strength of the bond between C1 and C1 binders (as measured by C1q binding) has been correlated with the ability of the binders to activate C1. The rate of activation of C1 has been studied by following the extent of hydrolysis of the C1r and C1s subcomponents, using a purified preparation of C1 labelled with 125I. The rate of activation of C1 was not correlated with the binding strength between C1q and the C1 binders. Immune complexes were found to activate C1 rapidly, whereas glutaraldehyde-aggregated IgG failed to activate faster than the spontaneous activation seen on incubation of C1 alone; the strength of the bond between C1q and the binders was similar in the two cases. It is suggested that an interaction other than the binding between C1q and C1 binders is necessary for activation of C1. C1 bound to immune complexes was not activated in the presence of C1 inhibitor, indicating that the inhibitor can prevent the hydrolysis of C1r under the test conditions.