Mechanism of activation of the classical pathway of complement by monoclonal IgE (DES). Restricted regulation of C4b by C4b-binding protein.
A human monoclonal IgE from patient DES, IgE (DES), has been shown to activate the classical pathway of complement. The mechanism of this activation has been investigated and can be summarized as follows: (a) IgE (DES) is able to bind and activate C1 in a dose-dependent fashion. This activation increases with the size of the aggregates used, but the affinity of C1 for IgE (DES) is weaker than for IgG. (b) A classical pathway C3 convertase can be assembled on IgE (DES) using purified C1, C4 and C2. The formation decay of this convertase is similar to that formed on IgG with an half-life of 9 min at 37 degrees C. (c) The extrinsic regulation of the C3 convertase by C4bp is restricted on IgE (DES) as compared to IgG. This restriction is shown on both the formation and the decay of the convertase. The mechanism of activation of the classical pathway of complement by IgE (DES) thus present some similarities with the assembly of the C3 convertase by the alternative pathway.
D000911:Antibodies, Monoclonal / Q000502:physiology; D001666:Binding Sites, Antibody; D002352:Carrier Proteins / Q000494:pharmacology*; D003167:Complement Activation; D003172:Complement C1 / Q000378:metabolism; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000494:pharmacology; D003181:Complement C4 / Q000378:metabolism*; D015935:Complement C4b; D003171:Complement Pathway, Classical; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000502:physiology*; D016167:Integrin alphaXbeta2; D007700:Kinetics
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D003172:Complement C1; D003180:Complement C3b Inactivator Proteins; D003181:Complement C4; D016167:Integrin alphaXbeta2; D007073:Immunoglobulin E; D015935:Complement C4b; D050577:Complement C3-C5 Convertases