...
首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Landscape of variable domain of heavy-chain-only antibody repertoire from alpaca
【24h】

Landscape of variable domain of heavy-chain-only antibody repertoire from alpaca

机译:从羊驼的重链抗体曲目的可变结构域的景观

获取原文
获取原文并翻译 | 示例
           

摘要

Heavy-chain-only antibodies (HCAbs), which are devoid of light chains, have been found naturally occurring in various species including camelids and cartilaginous fish. Because of their high thermostability, refoldability and capacity for cell permeation, the variable regions of the heavy chain of HCAbs (VHHs) have been widely used in diagnosis, bio-imaging, food safety and therapeutics. Most immunogenetic and functional studies of HCAbs are based on case studies or a limited number of low-throughput sequencing data. A complete picture derived from more abundant high-throughput sequencing (HTS) data can help us gain deeper insights. We cloned and sequenced the full-length coding region of VHHs in Alpaca (Vicugna pacos) via HTS in this study. A new pipeline was developed to conduct an in-depth analysis of the HCAb repertoires. Various critical features, including the length distribution of complementarity-determining region 3 (CDR3), V(D)J usage, VJ pairing, germline-specific mutation rate and germline-specific scoring profiles (GSSPs), were systematically characterized. The quantitative data show that V(D)J usage and VHH recombination are highly biased. Interestingly, we found that the average CDR3 length of classical VHHs is longer than that of non-classical ones, whereas the mutation rates are similar in both kinds of VHHs. Finally, GSSPs were built to quantitatively describe and compare sequences that originate from each VJ pair. Overall, this study presents a comprehensive landscape of the HCAb repertoire, which can provide useful guidance for the modeling of somatic hypermutation and the design of novel functional VHHs or VHH repertoires via evolutionary profiles.
机译:仅在包括骆驼虫和软骨鱼类在内的各种物种中发现,仅具有轻链的重链抗体(HCABs),其天然存在于包括骆驼和软骨的各种物种中。由于它们的高热稳定性,可重折叠性和细胞渗透能力,HCABs(VHHS)重链的可变区已被广泛用于诊断,生物成像,食品安全和治疗方法。 HCAB的大多数免疫发生和功能性研究基于案例研究或有限数量的低通量测序数据。从更丰富的高吞吐量排序(HTS)数据导出的完整图片可以帮助我们获得更深入的见解。我们在本研究中通过HTS克隆并测序了alpaca(viCugna Pacos)的vhhs的全长编码区。开发了一种新的管道,以对HCAB曲目进行深入分析。系统地表征了各种关键特征,包括互补确定区域3(CDR3),V(D)J使用,VJ配对,特异性突变率和种质特异性评分率(GSSP)的长度分布。定量数据显示V(D)J使用和VHH重组高度偏置。有趣的是,我们发现古典VHHS的平均CDR3长度比非古典VHHs的平均CDR3长度长,而突变率在这两种VHH中都相似。最后,建立GSSP以定量描述和比较源自每个VJ对的序列。总体而言,本研究介绍了HCAB曲目的综合景观,可以通过进化型材为各体高原和新功能VHHS或VHH曲目的设计提供有用的指导。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号