Roux K H, Strelets L, Michaelsen T E
Department of Biological Science, Structural Biology Program, Florida State University, Tallahassee 32306, USA.
J Immunol. 1997 Oct 1;159(7):3372-82.
A variable region (Id)-matched set of genetically engineered human IgG1, -2, -3, and -4 subclass molecules was analyzed by electron microscopy for hinge-mediated differences in flexibility. The hinge-mediated bending was studied, as was the ability of the subclasses to form immune complexes with two anti-Id mAbs. The data show that the rank order (most to least flexible) of the IgG subclasses for hinge-folding mode of flexibility between Fab arms is IgG3 > IgG1 > IgG4 > IgG2. The mean Fab-Fab angles for the subclasses are IgG3, 136 degrees; IgG4, 128 degrees; IgG2, 127 degrees; and IgG1, 117 degrees. Fab-Fc angles were similarly analyzed. By sampling of equimolar mixtures of Id-bearing IgGs and each of two anti-Id mAb after incubation over time (1.5 min to 3.5 h), different kinetic profiles of immune complex formation of defined geometry were documented. Both anti-Id mAbs displayed unique kinetic profiles when complexed with the four IgG subclass molecules but also shared important features. Most notable was the higher propensity to form closed bivalent ring Id-anti-Id dimers with IgG3 than with IgG2 and IgG4. IgG1 was intermediate in its ability to form such dimers.
通过电子显微镜分析了一组与可变区（Id）匹配的基因工程人IgG1、-2、-3和-4亚类分子，以研究铰链介导的柔韧性差异。研究了铰链介导的弯曲以及亚类与两种抗Id单克隆抗体形成免疫复合物的能力。数据表明，就Fab臂之间铰链折叠模式的柔韧性而言，IgG亚类的柔韧性排序（从最灵活到最不灵活）为IgG3 > IgG1 > IgG4 > IgG2。各亚类的平均Fab-Fab角分别为：IgG3为136度；IgG4为128度；IgG2为127度；IgG1为117度。对Fab-Fc角进行了类似分析。通过对含Id的IgG与两种抗Id单克隆抗体之一的等摩尔混合物在不同时间（1.5分钟至3.5小时）孵育后进行取样，记录了具有特定几何形状的免疫复合物形成的不同动力学特征。两种抗Id单克隆抗体与四种IgG亚类分子形成复合物时均表现出独特的动力学特征，但也有一些重要的共同特征。最显著的是，与IgG2和IgG4相比，IgG3更倾向于形成封闭的二价环Id-抗Id二聚体。IgG1形成此类二聚体的能力处于中间水平。
