Abstract:
Camelids are the only mammals that can produce functional heavy-chain antibodies (HCAbs). Although HCAbs were discovered over 30 years ago, the antibody gene repertoire of Bactrian camels remains largely underexplored. To characterize the diversity of variable genes of HCAbs (VHHs), germline and rearranged VHH repertoires are constructed. Phylogenetics analysis shows that all camelid VHH genes are derived from a common ancestor and the nucleotide diversity of VHHs is similar across all camelid species. While species-specific hallmark sites are identified, the non-canonical cysteines specific to VHHs are distinct in Bactrian camels and dromedaries compared with alpacas. Though low divergence at the germline repertoire between wild and domestic Bactrian camels, higher expression of VHHs is observed in some wild Bactrian camels than that of domestic ones. This study not only adds our understanding of VHH repertoire diversity across camelids, but also provides useful resources for HCAb engineering.
摘要:
骆驼是唯一能够产生功能性重链抗体(HCAb)的哺乳动物。尽管HCAbs是30多年前发现的,双峰骆驼的抗体基因库在很大程度上仍未被开发。为了表征HCAbs(VHHs)可变基因的多样性,构建了种系和重排的VHH库。系统发育学分析表明,所有骆驼VHH基因都来自共同的祖先,并且所有骆驼物种的VHH的核苷酸多样性相似。虽然确定了特定物种的标志地点,与羊驼相比,双峰骆驼和单峰骆驼中VHHs特异性的非规范半胱氨酸是不同的。尽管野生和家养双峰骆驼之间的种系差异很小,在一些野生双峰骆驼中观察到VHHs的表达高于国内的。这项研究不仅增加了我们对骆驼科VHH库多样性的理解,但也为HCAb工程提供了有用的资源。