The classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. It is triggered by antigen-bound antibody molecules. It is the binding of a specific part of the antibody molecule to the C1 component that initiates this pathway.

This initial enzyme, C1, is a complex formed through a calcium-dependent association between two reversibly interacting subunits, C1q and C1r2s2. Approximately 70% of C1 is at all times present in this complex form. C1 occurs in serum as a proenzyme which tends to undergo autoactivation but which is strictly controlled by C1 inhibitor (C1-In or C1 esterase). Upon the binding of C1 to immune complexes by virtue of the affinity of C1q for immunoglobulins (specifically IgM and IgG), the controlling action of C1-In is overcome and C1q effects activation of C1r2s2.

C1q possesses no intrinsic catalytic activity, but when any of several activators bind to the C1q subcomponent of C1, the homologous C1r and C1s subcomponents are converted into catalytically active species, namely C1r* and C1s*, triggering the first step of the classical pathway of complement activation.

Thus, on binding to immune complexes through C1q, the subunits of C1 become firmly associated and autoactivation commences even in the presence of the Cl-In. Initially, a conformational change in C1r occurs, followed by proteolytic activation which results in the cleavage of all four polypeptide chains of C1r2s2. The two activated C1s subunits are then able to catalyse the assembly of the C3 convertase, C4b2a, which has been formed from C2 and C4.

See Also

• Alternate complement pathway