Interaction of human C1q with IgG and IgM: revisited.

The first step of activation of the classical complement pathway involves the binding of the globular C1q domain (gC1q) to the antigen-bound IgG or IgM. To improve our understanding of the mechanism of interaction of gC1q with IgG and IgM, we compared the immunoglobulin binding properties of single-residue mutants of individual globular modules of A and C chains. We found that Lys(A200) and Lys(C170) are significant for binding with both immunoglobulins.

Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q.

C1q is the first subcomponent of the classical complement pathway that binds antigen-bound IgG or IgM and initiates complement activation via association of serine proteases C1r and C1s. The globular domain of C1q (gC1q), which is the ligand-recognition domain, is a heterotrimeric structure composed of the C-terminal regions of A (ghA), B (ghB), and C (ghC) chains. The expression and functional characterization of ghA, ghB, and ghC modules have revealed that each chain has some structural and functional autonomy.