PDF(Pubmed)
Abstract：
The constant region of the immunoglobulin (IG) or antibody heavy gamma chain is frequently engineered to modify the effector properties of the therapeutic monoclonal antibodies. These variants are classified in regards to their effects on effector functions, antibody-dependent cytotoxicity (ADCC), antibody-dependent phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) enhancement or reduction, B cell inhibition by the coengagement of antigen and FcγR on the same cell, on half-life increase, and/or on structure such as prevention of IgG4 half-IG exchange, hexamerisation, knobs-into-holes and the heteropairing H-H of bispecific antibodies, absence of disulfide bridge inter H-L, absence of glycosylation site, and site-specific drug attachment engineered cysteine. The IMGT engineered variant identifier is comprised of the species and gene name (and eventually allele), the letter \'v\' followed by a number (assigned chronologically), and for each concerned domain (e.g, CH1, h, CH2 and CH3), the novel AA (single letter abbreviation) and IMGT position according to the IMGT unique numbering for the C-domain and between parentheses, the Eu numbering. IMGT engineered variants are described with detailed amino acid changes, visualized in motifs based on the IMGT numbering bridging genes, sequences, and structures for higher order description.
摘要：
免疫球蛋白(IG)或抗体重γ链的恒定区经常被工程化以修饰治疗性单克隆抗体的效应物特性。这些变体根据它们对效应子功能的影响进行分类，抗体依赖性细胞毒性（ADCC），抗体依赖性吞噬作用（ADCP），补体依赖性细胞毒性（CDC）增强或减少，通过抗原和FcγR在同一细胞上的共同参与抑制B细胞，在半衰期增加时，和/或在诸如防止IgG4半IG交换的结构上，hexamerisation,旋钮入孔和双特异性抗体的异质配对H-H，H-L间不存在二硫键，没有糖基化位点，和位点特异性药物连接工程半胱氨酸。IMGT工程变体标识符由物种和基因名称（最终是等位基因）组成，字母\'v\'后跟一个数字（按时间顺序分配），和每个相关域(e.g,CH1,h,CH2和CH3)，根据C域的IMGT独特编号以及括号之间的新颖AA（单字母缩写）和IMGT位置，欧盟编号。IMGT工程变体描述了详细的氨基酸变化，在基于IMGT编号桥接基因的基序中可视化，序列，和结构的高阶描述。
