Chimeric mouse human IgG3 antibodies with an IgG4-like hinge region induce complement-mediated lysis more efficiently than IgG3 with normal hinge.
We have altered the amino acid sequence of the hinge and the first constant domain (CH1) of mouse/human chimeric IgG3 antibodies by site-directed mutagenesis, so as to make the sequences identical to those of IgG4. All the mutant antibodies with altered hinge region were more active in complement activation and complement-mediated lysis than native IgG3. The mutations in CH1, however, did not alter the activity. This demonstrates the importance of the hinge region in modulating this effector function. The results show that the primary structure of neither CH1 nor the hinge of IgG4 is responsible for the lack of complement activation shown by this subclass.
Department of Biology, University of Oslo, Norway.
L
L
Norderhaug
O H
OH
Brekke
B
B
Bremnes
R
R
Sandin
A
A
Aase
T E
TE
Michaelsen
I
I
Sandlie
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003167:Complement Activation; D015922:Complement C1q / Q000378:metabolism; D003196:Computer Graphics; D003602:Cytotoxicity, Immunologic; D004252:DNA Mutational Analysis; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D009841:Oligonucleotides / Q000737:chemistry; D011993:Recombinant Fusion Proteins; D013329:Structure-Activity Relationship
D007074:Immunoglobulin G; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; D015922:Complement C1q