PathwayStep6809 PathwayStep6812 Creation of C4 and C2 activators Authored: de Bono, B, 2004-08-04 09:17:50 Pubmed11044372 Pubmed12396008 Pubmed70787 Reactome Database ID Release 43166786 Reactome, http://www.reactome.org ReactomeREACT_8012 Reviewed: D'Eustachio, P, 2006-07-03 21:35:13 Two pathways lead to a complex capable of activating C4 and C2. The classical pathway is triggered by activation of the C1-complex (C1q, 2X C1r and 2X C1s, thus forming C1qr2s2). This occurs when C1q binds to IgM or IgG complexed with antigens, a single IgM can initiate the pathway while multiple IgGs are needed, or when C1q binds directly to the surface of the pathogen. Binding leads to conformational changes in C1q, activating the serine protease activity of C1r, which then cleaves C1s, another serine protease. The C1r2s2 component is now capable of splitting C4 and C2 to produce the classical C3-convertase C4b2a. C1r and C1s are additionally controlled by C1-inhibitor. The lectin pathway is similar in operation but has different components. Mannose-binding lectin (MBL) initiates the lectin pathway cascade by binding to specific carbohydrate patterns on pathogenic cell surfaces. MASPs associated with MBL become activated and capable of C4 and C2 cleavage, giving rise to the same C3 convertase C4b-C2a as the classical pathway. Lectin pathway of complement activation Classical antibody-mediated complement activation