Human IgG3 can adopt the disulfide bond pattern characteristic for IgG1 without resembling it in complement mediated cell lysis.
In this paper we describe the construction of mouse-human IgG3 mutant antibodies resembling IgG1 in their disulfide bond pattern between the heavy and light chain (H-L) and between the two heavy chains (H-H). The effector functions of these mutant antibodies were compared to normal IgG3 and IgG1. Changing only the disulfide bond pattern between the heavy and light chains did not alter the ability to induce complement mediated cell lysis (CML), regardless of the amount of corresponding antigen that had been introduced to the surface of the target cells. However, alteration of the disulfide bond pattern between the two heavy chains had a large effect on CML due to shortening of the hinge from 62 to 15 amino acids. No difference between the mutants and normal antibodies in antibody-dependent cell-mediated cytotoxicity (ADCC) was observed. This suggests that IgG3 can adopt the H-L disulfide bond pattern of IgG1 without obtaining the CML activity characteristic for IgG1.
Brekke
O H
OH
Department of Biology, University of Oslo, Norway.
Bremnes
B
B
Sandin
R
R
Aase
A
A
Michaelsen
T E
TE
Sandlie
I
I
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000235:genetics*; D000920:Antibody-Dependent Cell Cytotoxicity; D001483:Base Sequence; D003165:Complement System Proteins / Q000494:pharmacology*; D004220:Disulfides / Q000737:chemistry*; D005803:Genes, Immunoglobulin; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000906:Antibodies; D004220:Disulfides; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D003165:Complement System Proteins