Generation of a chickenized catalytic anti-nucleic acid antibody by complementarity-determining region grafting
| Autor: | Youngsil Seo, Myung-Hee Kwon, Keun Woo Lee, Jae-Ho Lee, Minjae Kim, Songmi Kim, Jin-Kyoo Kim, Yuno Lee, Sung June Byun, Jooho Roh |
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| Rok vydání: | 2015 |
| Předmět: |
animal structures
Molecular Sequence Data Immunology Immunoglobulins Enzyme-Linked Immunosorbent Assay Complementarity determining region Antibodies Catalysis Mice chemistry.chemical_compound Nucleic Acids Animals Humans Amino Acid Sequence Molecular Biology Peptide sequence Polyacrylamide gel electrophoresis biology Immunogenicity Complementarity Determining Regions Molecular biology Anti-DNA Antibody chemistry biology.protein Nucleic acid Electrophoresis Polyacrylamide Gel Antibody Chickens DNA HeLa Cells Single-Chain Antibodies |
| Zdroj: | Molecular Immunology. 63:513-520 |
| ISSN: | 0161-5890 |
| Popis: | In contrast to a number of studies on the humanization of non-human antibodies, the reshaping of a non-human antibody into a chicken antibody has never been attempted. Therefore, nothing is known about the animal species-dependent compatibility of the framework regions (FRs) that sustain the appropriate conformation of the complementarity-determining regions (CDRs). In this study, we attempted the reshaping of the variable domains of the mouse catalytic anti-nucleic acid antibody 3D8 (m3D8) into the FRs of a chicken antibody (“chickenization”) by CDR grafting, which is a common method for the humanization of antibodies. CDRs of the acceptor chicken antibody that showed a high homology to the FRs of m3D8 were replaced with those of m3D8, resulting in the chickenized antibody (ck3D8). ck3D8 retained the biochemical properties (DNA binding, DNA hydrolysis, and cellular internalizing activities) and three-dimensional structure of m3D8 and showed reduced immunogenicity in chickens. Our study demonstrates that CDR grafting can be applied to the chickenization of a mouse antibody, probably due to the interspecies compatibility of the FRs. |
| Databáze: | OpenAIRE |
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