ABSTRACT
Complement is a group of serum proteins that play a vital role in host defense against infection. Activation of the complement system triggers sequential biochemical reactions, which are accompanied by the generation of numerous biologically active mediators of inflammation, ultimately leading to the destruction and clearance of invading organisms. The classical pathway of complement is initiated by the first complement component (Cl).* After an activating substance, such as an immune complex, binds and activates C l , C1 then activates the second (C2) and fourth (C4) complement components thereby triggering the complement cascade. The purpose of this report is to summarize the known molecular principles involved in C 1 activation and its physiologic control, while emphasizing contemporary aspects. Other recent reviews dealing with C1 are by Cooper,' Lachmann and HughesJ o n e ~ , ~ Colomb et al. ,3 and S~humaker.~ C1 is of interest not only because of its importance as the initiator of the classical complement pathway, but also since it is the most readily defined and easily studied mediator of immunoglobulin function. Furthermore, C1 in itself is an intriguing biochemical model involving specific protein-protein interactions, induced conformational changes and activation by limited proteolysis (Figure 1).
