Properdin, Human, mAb 2.9
The monoclonal antibody 2.9 reacts with human properdin (factor P), which is a single-chain plasmaglycoprotein with an apparent molecular mass of 52-55 kDa, The protein domain structure ofproperdin consists of six thrombospondin repeat sequences between short N- and C-terminaldomains. In blood, properdin exists as a mixture of head-to-tail dimers, trimers and tetramers. Theprotein is expressed by a variety of leukocytes, including monocytes, T lymphocytes and neutrophils,but also by endothelial cells in which properdin synthesis is induced by certain stress factors.Properdin participates in the alternative pathway of complement activation together with C3 andfactors B, D, I and H by prolonging the half-life of the labile C3bBb, which is deposited on immunecomplexes or foreign surfaces. This permits amplification of C3bBb formation in competition withcatabolism of C3b by factor I, which uses factor H as a cofactor. The local amplification process leadsto the creation of the alternative pathway C5 convertase, C3bBb3b, and initiates the terminal pathwayof complement activation. As a consequence, properdin is consumed by binding to C3bBb, whichshows an order of preference of tetramers over trimers over dimers, which corresponds to thefunctional activity of the oligomeric forms. Deficiency or malfunction of the molecule may lead tosevere impairment of alternative pathway activation, depending on the precise nature of the defect.Three types of deficiencies have been described so far: type 1 (or I) is characterised by serum withvery low or absent properdin activity in hemolytic assays and <0.1 µg/ml immunoreactive protein; type 2 (or II) is characterised by low but detectable levels of immunoreactive protein (>2 µg/ml) andimpairment of some, but not all functional test, and type 3 (or III) has normal levels of immunoreactivebut dysfunctional protein (5-25 µg/mL). Lower properdin levels were found in 70% of diabetic patientswhen compared to nondiabetic controls and is suggested by the authors that patients with lowexpression of properdin take preventive measures and early treatments against infection. Themonoclonal antibody 2.9 is suitable for functional studies as well as use in immunoassays.
