The RmC7H8 monoclonal antibody specifically recognizes the C1q component of the mouse macromolecular C1 complex. The complex is comprised of C1q and 2 molecules each of the serine proteases, C1r and C1q. The C1 macromolecular complex, C1qC1r2C1s2, is bound together by Ca2+ ions. C1q is a serum protein that is synthesized by macrophages and microglia. It exists as an ~460 kDa protein formed from 18 polypeptide chains comprised of three different subunits named C1qa, C1qb, and C1qc. Each chain contains an N-terminal collagen-like sequence and a C-terminal globular gC1q module. Structural studies reveal that C1q is formed as a hexamer with 6 collagen-like triple helices, forming a central fiber bundle, each extended by globular domains. C1q is a multifunctional protein that can regulate a variety of cellular processes in addition to activating the classical complement pathway (CCP). C1q globular regions mediate target recognition such as binding to the Fc regions of IgG and IgM antibodies found in immune complexes including antibodies bound to pathogens or target cells and subsequent activation of the CCP. The C1q globular regions can also bind to bacterial and viral surface proteins as well as altered self elements including histones, DNA, and annexins on the surface of apoptotic or necrotic cells. The enhanced phagocytosis mediated through interaction of bound C1q with various receptors expressed by phagocytes, possibly combined with further complement activation and opsonization of cells, may contribute to the safe removal of stressed or dead cells that are pro-inflammatory. Conformational changes in target bound C1q's collagen-like regions can lead to interaction with and activation of the C1r and C1s proteases which result in activation of the CCP.
