The complement system plays important roles in both innate and adaptive immune response and can produce an inflammatory and protective reaction to challenges from pathogens.
Complement C5 is a central molecule in all three pathways and after cleavage by its convertases, it initiates the terminal pathway in order to generate the cytolytic MAC.C5 is mainly synthesised in the liver as a single polypeptide chain and is present in serum in a concentration of 50-80 μm/ml. Besides, local synthesis of C5 is also supported by other cell types including monocytes/macrophages, neutrophils, fibroblasts, and astrocytes. Before secretion the molecule is glycosylated and secreted into plasma as a 190 kDa glycoprotein consisting of a disulphide linked alpha-chain (111 kDa) and beta-chain (75 kDa).
The complement has become an interesting therapeutic target. Especially after the success of Eculizumab, a monoclonal antibody against C5, in the treatment for aHUS and PNH and the application in clinical trials for many other diseases. Monoclonal antibody #10B6 is human specific and acts as an equivalent of Eculizumab. The antibody recognizes the beta chain and competes for binding to the same epitope as Eculizumab. It shows high binding to C5 with a negligible off rate.
Besides C5 the antibody also recognizes C5b6, but not C6. Using haemolytic assays shows efficient inhibition of AP as well as CP, with a comparable dose-response curve to Eculizumab in the CP.Antibody #10B6 has been tested in western blotting, ELISA and functional studies (Ref. 1)
Functional studies, Immuno assays