Iconic Therapeutics, South San Francisco, CA, United States of America.
PLoS One. 2019 Jul 19;14(7):e0219999. doi: 10.1371/journal.pone.0219999. eCollection 2019.
While pigs and rabbits are used as models for human immune diseases, FcγR binding is poorly characterized in both test species. To evaluate antibody binding to FcγRIIIA, a receptor involved in antibody-dependent cellular cytotoxicity, chimerized antibodies were generated by grafting the variable regions of a human IgG1 onto scaffolds from both species. The affinities of the parent and chimeric antibodies to the FcγRIIIA proteins from all three species were determined. While the human IgG1 and rabbit IgG had similar affinities for each FcγRIIIA with notable differences across species, pig IgG1 only bound pig FcγRIIIA with appreciable affinity. Also, the functional pig and rabbit proteins described here can be used in future experiments, such as pharmacology and mechanism of action studies.
虽然猪和兔子被用作人类免疫疾病的模型，但这两种实验动物的 FcγR 结合情况描述得并不完善。为了评估抗体与 FcγRIIIA 的结合情况，后者是一种参与抗体依赖的细胞毒性的受体，我们通过将人 IgG1 的可变区嫁接到来自这两种动物的支架上来生成嵌合抗体。确定了亲本抗体和嵌合抗体与来自所有三种物种的 FcγRIIIA 蛋白的亲和力。虽然人 IgG1 和兔 IgG1 对每种 FcγRIIIA 的亲和力相似，但在物种间存在显著差异，而猪 IgG1 仅与猪 FcγRIIIA 具有可察觉的亲和力。此外，本文中描述的功能性猪和兔蛋白可用于未来的实验，如药理学和作用机制研究。
