Kim Jin Hong, Hong Hyo Jeong
Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Gangwon-do, Korea.
Methods Mol Biol. 2012;907:237-45. doi: 10.1007/978-1-61779-974-7_13.
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.
人源化抗体通过互补决定区（CDR）移植构建，同时保留那些影响抗原结合活性的鼠源框架残基。为降低CDR移植人源化抗体的免疫原性，通过超变区（SDR）移植将CDR移植人源化抗体中的鼠源成分降至最低。在每个CDR内，有更多直接参与与抗原相互作用的可变位置，即特异性决定残基（SDR），而有更多保守残基维持CDR环的构象。SDR可从抗原-抗体复合物的三维结构和/或CDR的突变分析中鉴定出来。通过将SDR和维持CDR构象的残基移植到人源模板上构建SDR移植人源化抗体，并通过测量其对用亲本抗体免疫的患者血清的反应性来评估其免疫原性潜力。
