Humanization by CDR grafting and specificity-determining residue grafting.
Humanized antibodies are constructed by CDR grafting, while retaining those murine framework residues that influence the antigen-binding activity. To reduce the immunogenicity of CDR-grafted humanized antibodies, the murine content in the CDR-grafted humanized antibodies is minimized through SDR grafting. Within each CDR, there are more variable positions that are directly involved in the interaction with antigen, i.e., specificity-determining residues (SDRs), whereas there are more conserved residues that maintain the conformations of CDRs loops. SDRs may be identified from the 3D structure of the antigen-antibody complex and/or the mutational analysis of the CDRs. An SDR-grafted humanized antibody is constructed by grafting the SDRs and the residues maintaining the conformations of the CDRs onto human template, and its immunogenic potential is evaluated by measuring the reactivity to the sera from patients who had been immunized with the parental antibody.
Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Gangwon-do, Korea.
Jin Hong
JH
Kim
Hyo Jeong
HJ
Hong
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000737:chemistry; D001667:Binding, Competitive; D022801:Complementarity Determining Regions / Q000276:immunology*; D004252:DNA Mutational Analysis; D057809:HEK293 Cells; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D008967:Molecular Biology / Q000379:methods*
D061067:Antibodies, Monoclonal, Humanized; D000936:Antigen-Antibody Complex; D022801:Complementarity Determining Regions; D007106:Immune Sera