title: Comparative Analysis of Immune Repertoires between Bactrian Camel's Conventional and Heavy-Chain Antibodies.
abstract: Compared to classical antibodies, camel heavy chain antibodies (HCAbs) are smaller in size due to lack of the light chain and the first constant domain of the heavy chain (CH1 region). The variable regions of HCAbs (VHHs) are more soluble and stable than that of conventional antibodies (VHs). Even with such simple structure, they are still functional in antigen binding. Although HCAbs have been extensively investigated over the past two decades, most efforts have been based upon low throughput sequence analysis, and there are only limited reports trying to analyze and describe the complete immune repertoire (IR) of camel HCAbs. Here we leveraged the high-throughput data generated by Next Generation Sequencing (NGS) of the variable domains of the antibody heavy chains from three Bactrian camels to conduct in-depth comparative analyses of the immunoglobulin repertoire. These include analyses of the complementary determining region 3 (CDR3) length and distribution, mutation rate, antibody characteristic amino acids, the distribution of the cysteine (Cys) codons, and the non-classical VHHs. We found that there is higher diversity in the CDR2 than in the other sub-regions, and there is a higher mutation rate in the VHHs than in the VHs (P < 0.05). In addition to substitutions at amino acid (AA) residue positions NO.49/50/52 between VH and VHH clones, we also observed other substitutions at the positions NO.40/54/57/96/101 that could lead to additional structural alterations. We also found that VH-derived VHH clones, referred to as non-classical VHH clones in this study, accounted for about 8% of all clones. Further, only 5%-10% clones had the Trp > Arg AA substitution at the first position of framework 4 for all types of clones. We present, for the first time, a relatively complete picture of the Bactrian camel antibody immune repertoire, including conventional antibody (Ab) and HCAbs, using PCR and in silico analysis based on high-throughput NGS data.
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Xinyang
authors: X
authors: Li
authors: Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.|Key Laboratory of Industrial Biotechnology of Guangdong Higher Education Institutes, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.|Pre-Incubator for Innovative Drugs & Medicine, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors: Xiaobo
authors: X
authors: Duan
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Kai
authors: K
authors: Yang
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Wei
authors: W
authors: Zhang
authors: Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.|Key Laboratory of Industrial Biotechnology of Guangdong Higher Education Institutes, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.|Pre-Incubator for Innovative Drugs & Medicine, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors: Changjiang
authors: C
authors: Zhang
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Longfei
authors: L
authors: Fu
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Zhe
authors: Z
authors: Ren
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Changxi
authors: C
authors: Wang
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Jinghua
authors: J
authors: Wu
authors: Zhangye City Bureau of Animal Husbandry and Veterinary, Zhangye, Gansu, 734000, China.
authors: Ruxue
authors: R
authors: Lu
authors: Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.|Key Laboratory of Industrial Biotechnology of Guangdong Higher Education Institutes, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.|Pre-Incubator for Innovative Drugs & Medicine, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors: Yanrui
authors: Y
authors: Ye
authors: Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors: Mengying
authors: M
authors: He
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Chao
authors: C
authors: Nie
authors: BGI-Shenzhen, Shenzhen 518083, China.
authors: Naibo
authors: N
authors: Yang
authors: BGI-Shenzhen, Shenzhen 518083, China.|James D. Watson Institute of Genome Sciences, Hangzhou 310058, China.
authors: Jian
authors: J
authors: Wang
authors: BGI-Shenzhen, Shenzhen 518083, China.|James D. Watson Institute of Genome Sciences, Hangzhou 310058, China.
authors: Huanming
authors: H
authors: Yang
authors: BGI-Shenzhen, Shenzhen 518083, China.|Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark.
authors: Xiao
authors: X
authors: Liu
authors: Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.|Key Laboratory of Industrial Biotechnology of Guangdong Higher Education Institutes, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.|Pre-Incubator for Innovative Drugs & Medicine, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors: Wen
authors: http://orcid.org/0000-0003-2272-0861
authors: W
authors: Tan
mesh_terms: D000818:Animals; D002162:Camelus; D005803:Genes, Immunoglobulin; D059014:High-Throughput Nucleotide Sequencing; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region