Inhibition of the classical activation pathway of complement-mediated lysis by monoclonal antibodies to complement components C3c and C3d.
Eight epitope-mapped monoclonal antibodies (MoAbs) to complement component C3d and five to complement component C3c were investigated to determine whether they could inhibit the classical activation pathway of complement-mediated lysis (CML) by using blood group AB red cells sensitized by A or B MoAbs. Three IgM C3d MoAbs and one IgG1 C3c MoAb were able to inhibit CML in a dose-dependent manner. In the presence of excess complement, no inhibition was observed. The greatest inhibition was observed with two high-affinity IgM antibodies that were specific for epitope 1 on the C3d component. Some inhibition was observed with a high-affinity IgM antibody specific for epitope 3 of the C3d component and also with a lower-affinity IgG antibody specific for epitope 1 of the C3c component. The results indicate that some complement MoAbs have the capacity to distinguish between conformationally and/or functionally different forms of red cell-bound C3.
Mushens
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International Blood Group Reference Laboratory, South Western Regional Transfusion Centre, Bristol, UK.
Bakacs
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D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D015932:Complement C3c / Q000276:immunology*; D015933:Complement C3d / Q000276:immunology*; D003171:Complement Pathway, Classical / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D006801:Humans
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015932:Complement C3c; D015933:Complement C3d