C1Q

C1q is the recognition subcomponent of the C1 complex in the classical pathway of the complement system. It is a large multimeric molecule that detects immune complexes and other targets, initiating the classical cascade. Structurally, C1q is composed of six heterotrimeric subunits (A, B, and C chains) arranged in a bouquet-like assembly, with each subunit containing a collagen-like stalk and a globular head (gC1q) that mediates ligand binding. The human C1q polypeptides are encoded by C1QA, C1QB, and C1QC, and together form a hexameric molecule associated with two serine proteases, C1r and C1s, to form the C1 complex. Upon binding to an antigen–antibody complex or to certain ligands such as C-reactive protein or apoptotic cells, C1q triggers activation of C1r and C1s, leading to proteolysis of C4 and C2 and formation of the C4b2a C3 convertase. This initiates the downstream complement cascade, resulting in opsonization, inflammation, and eventual lysis or phagocytosis of targets. Beyond activation, C1q participates in clearance of immune complexes and apoptotic cells and can modulate inflammatory responses through receptor interactions on immune cells. It also recognizes a variety of ligands beyond antibodies, enabling it to bridge innate and adaptive immunity and to contribute to tissue homeostasis.

Clinical relevance: C1q deficiency is rare but strongly associated with systemic lupus erythematosus. Defects or autoantibodies against C1q can contribute to disease, and deposition of C1q in tissues may occur in certain glomerulopathies. Dysregulation of C1q function has implications for autoimmunity and inflammation.