恒定结构域影响鼠源人嵌合抗体与炭疽芽孢杆菌荚膜多肽的结合。
Constant domains influence binding of mouse-human chimeric antibodies to the capsular polypeptide of Bacillus anthracis.
机构信息
Department of Microbiology and Immunology; University of Nevada School of Medicine, Reno, NV, USA.
出版信息
Virulence. 2013 Aug 15;4(6):483-8. doi: 10.4161/viru.25711. Epub 2013 Jul 17.
Abstract
Our laboratory previously described the binding characteristics of the murine IgG3 monoclonal antibody (MuAb) F26G3. This antibody binds the poly-glutamic acid capsule (PGA) of Bacillus anthracis, an essential virulence factor in the progression of anthrax. F26G3 IgG3 MuAb binds PGA with a relatively high functional affinity (10 nM), produces a distinct "rim" quellung reaction, and is protective in a murine model of pulmonary anthrax. This study engineered an IgG subclass family of F26G3 mouse-human chimeric antibodies (ChAb). The F26G3 ChAbs displayed 9- to 20-fold decreases in functional affinity, as compared with the parent IgG3 MuAb. Additionally, the quellung reactions that were produced by the ChAbs all differed from the parent IgG3 MuAb in that they appeared "puffy" in nature. This study demonstrates that human constant domains may influence multiple facets of antibody binding to microbial capsular antigens despite their spatial separation from the traditional antigen-binding site.
摘要
我们实验室之前描述了鼠源 IgG3 单克隆抗体（MuAb）F26G3 的结合特性。这种抗体与炭疽杆菌的多聚谷氨酸荚膜（PGA）结合，PGA 是炭疽病进展过程中的一个重要毒力因子。F26G3 IgG3 MuAb 与 PGA 的结合具有相对较高的功能亲和力（10 nM），产生明显的“边缘”沉淀反应，并在炭疽肺的小鼠模型中具有保护作用。本研究构建了 F26G3 小鼠-人嵌合抗体（ChAb）的 IgG 亚类家族。与亲本 IgG3 MuAb 相比，F26G3 ChAb 的功能亲和力降低了 9-20 倍。此外，ChAb 产生的沉淀反应在本质上与亲本 IgG3 MuAb 不同，它们呈现出“肿胀”的特性。本研究表明，尽管人类恒定区与传统抗原结合位点空间分离，但它们可能影响抗体与微生物荚膜抗原结合的多个方面。
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