体细胞突变
生物
计算生物学
互补决定区
生殖系
亲和力成熟
免疫球蛋白轻链
遗传学
突变率
重链
抗体库
互补性(分子生物学)
基因
抗体
B细胞
作者
Zhui Tu,Xiaoqiang Huang,Jinheng Fu,Na Hu,Wei Zheng,Yanping Li,Yang Zhang
出处
期刊:Immunology
[Wiley]
日期:2020-06-30
卷期号:161 (1): 53-65
被引量:23
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.
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