A comprehensive profiling of T- and B-lymphocyte receptor repertoires from a Chinese-origin rhesus macaque by high-throughput sequencing

PLoS One. 2017 Aug 16;12(8):e0182733. doi: 10.1371/journal.pone.0182733. eCollection 2017.

Abstract

Due to the close genetic background, high similarity of physiology, and susceptibility to infectious and metabolic diseases with humans, rhesus macaques have been widely used as an important animal model in biomedical research, especially in the study of vaccine development and human immune-related diseases. In recent years, high-throughput sequencing based immune repertoire sequencing (IR-SEQ) has become a powerful tool to study the dynamic adaptive immune responses. Several previous studies had analyzed the responses of B cells to HIV-1 trimer vaccine or T cell repertoire of rhesus macaques using this technique, however, there are little studies that had performed a comprehensive analysis of immune repertoire of rhesus macaques, including T and B lymphocytes. Here, we did a comprehensive analysis of the T and B cells receptor repertoires of a Chinese rhesus macaque based on the 5'-RACE and IR-SEQ. The detailed analysis includes the distribution of CDR3 length, the composition of amino acids and nucleotides of CDR3, V, J and V-J combination usage, the insertion and deletion length distribution and somatic hypermutation rates of the framework region 3 (FR3). In addition, we found that several positions of FR3 region have high mutation frequencies, which may indicate the existence of new genes/alleles that have not been discovered and/or collected into IMGT reference database. We believe that a comprehensive profiling of immune repertoire of rhesus macaque will facilitate the human immune-related diseases studies.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Composition
  • Cluster Analysis
  • Complementarity Determining Regions / genetics
  • DNA Mutational Analysis
  • Female
  • Gene Expression Profiling*
  • Gene Frequency
  • High-Throughput Nucleotide Sequencing*
  • INDEL Mutation
  • Macaca mulatta / genetics*
  • Macaca mulatta / immunology
  • Receptors, Antigen, B-Cell / genetics*
  • Receptors, Antigen, T-Cell / genetics*
  • Transcriptome*
  • V(D)J Recombination

Substances

  • Complementarity Determining Regions
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell

Grants and funding

XYL's work was supported by the Foundation of Shenzhen Science and Technology Innovation Committee (Project Number JCYJ20160531194232631). This study was also supported by BGI-Shenzhen Research Institute.