Analogous Interactions in Initiating Complexes of the Classical and Lectin Pathways of Complement

作者：Phillips Anna E; Toth Julia; Dodds Alister W; Girija Umakhanth Venkatraman; Furze Christopher M; Pala Eleni; Sim Robert B; Reid Kenneth B M; Schwaeble Wilhelm J; Schmid Ralf; Keeble Anthony H; Wallis Russell^*

来源：The Journal of Immunology, 2009, 182(12): 7708-7717.

DOI：10.4049/jimmunol.0900666

The classical and lectin pathways of complement activation neutralize pathogens and stimulate key immunological processes. Both pathways are initiated by collagen-containing, soluble pattern recognition molecules associated with specific serine proteases. In the classical pathway, C1q binds to Ab-Ag complexes or bacterial surfaces to activate C1and C1s. In the lectin pathway, mannan-binding lectin and ficolins bind to carbohydrates on pathogens to activate mannan-binding lectin-associated serine protease 2. To characterize the interactions leading to classical pathway activation, we have analyzed binding between human C1q, Or, and C1s, which associate to form C1, using full-length and truncated protease components. We show that C1r and C1s bind to C1q independently. The CUBI-epidermal growth factor fragments contribute most toward binding, but CUB2 of C1r, but not of C1s, is also important. Each C1rs tetramer presents a total of six binding sites, one for each of the collagenous domains of C1q. We also demonstrate that subcomponents of the lectin and classical pathways cross-interact. Thus, although the stoichiometries of complexes differ, interactions are analogous, with equivalent contacts between recognition and protease subcomponents. Importantly, these new data are contrary to existing models of C1 and enable us to propose a new model using mannan-binding lectin-mannan-binding lectin-associated serine protease interactions as a template. The Journal of Immunology, 2009,182: 7708-7717.

• 出版日期2009-6-15