McCloskey N, Turner M W, Steffner P, Owens R, Goldblatt D
Institute of Child Health, London, UK.
Immunology. 1996 Jun;88(2):169-73. doi: 10.1111/j.1365-2567.1996.tb00001.x.
Although antibody affinity is primarily determined by immunoglobulin variable region structure human IgG antibodies of the four subclasses specific for the same antigen have been shown to differ in their affinity. To explore the influence of the immunoglobulin constant region on functional antibody affinity, a set of V region identical mouse-human chimeric IgG subclasses specific for TAG72 (tumour-associated glycoprotein) were studied. Biomolecular interaction analysis (BIA) was used to determine the binding kinetics of whole IgG subclasses and F(ab')2 fragments. Despite identical V regions, binding kinetics differed for the four subclasses. The apparent dissociation rate constants of the intact immunoglobulins ranked IgG4 < IgG3 < IgG2 < IgG1. In contrast, analysis of the binding characteriztics of the F(ab')2 fragments derived from IgG1, IgG2 and IgG4 revealed identical binding kinetics. The structure of the constant regions of the humanized IgG subclass antibodies clearly influenced functional antibody affinity, as has been described for the murine IgG subclasses. The exact mechanism for this phenomenon remains obscure but such differences should be taken into account when designing or choosing antibodies for therapeutic use.
尽管抗体亲和力主要由免疫球蛋白可变区结构决定，但已表明针对同一抗原的四种亚类的人IgG抗体在亲和力上存在差异。为了探究免疫球蛋白恒定区对功能性抗体亲和力的影响，研究了一组针对TAG72（肿瘤相关糖蛋白）的V区相同的小鼠-人嵌合IgG亚类。采用生物分子相互作用分析（BIA）来确定完整IgG亚类和F(ab')2片段的结合动力学。尽管V区相同，但四种亚类的结合动力学不同。完整免疫球蛋白的表观解离速率常数排序为IgG4 < IgG3 < IgG2 < IgG1。相反，对源自IgG1、IgG2和IgG4的F(ab')2片段的结合特性分析显示结合动力学相同。如对鼠IgG亚类所描述的那样，人源化IgG亚类抗体恒定区的结构明显影响功能性抗体亲和力。这种现象的确切机制仍不清楚，但在设计或选择治疗用抗体时应考虑到这些差异。
