Activation of complement by human IgG1 and human IgG3 antibodies against the human leucocyte antigen CD52.
Activation of the complement cascade by immunoglobulin G (IgG) plays a major role in the host defense against pathogens. Using recombinant human antibodies specific for the leucocyte antigen CD52, different allotypes of human IgG1 subclass were compared for their ability to activate human complement. In addition the roles of the different length hinge regions of IgG1 and IgG3 were investigated. It was found that the naturally occurring allotypes G1m(a,z) and G1m(f), and one artificially created isoallotype, G1m(null), did not significantly differ in their overall ability to cause cell lysis. However, some differences in binding of individual components of the classical activation pathway were detected. More of the complement component C1s seemed to be associated with the allotype G1m(f), although this did not result in an overall improvement in lytic potency. In this system the wild-type IgG3 was found to be less effective in complement lysis than IgG1. By shortening the hinge region of IgG3 to resemble that of an IgG1 antibody, increased complement binding was observed compared with that of wild-type IgG3 and the IgG1 allotypes. The overall lytic potency of the antibody was also improved compared with wild type IgG3 and it was also slightly more effective than the IgG1 allotypes.
Redpath
S
S
Department of Pathology, University of Cambridge, UK.
Michaelsen
T
T
Sandlie
I
I
Clark
M R
MR
D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; D003167:Complement Activation / Q000276:immunology*; D015922:Complement C1q / Q000378:metabolism; D003173:Complement C1s / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D007129:Immunoglobulin Gm Allotypes / Q000276:immunology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D003176:Complement C3; D003181:Complement C4; D006023:Glycoproteins; D007074:Immunoglobulin G; D007129:Immunoglobulin Gm Allotypes; D015922:Complement C1q; D003173:Complement C1s