Development of a RACE-based RNA-Seq approach to characterize the T-cell receptor repertoire of porcine γδ T cells

Dev Comp Immunol. 2020 Apr:105:103575. doi: 10.1016/j.dci.2019.103575. Epub 2019 Dec 14.

Abstract

Recent data suggest that porcine γδ T cells exhibit a similar degree of functional plasticity as human and murine γδ T cells. Due to the high frequency of TCR-γδ+ cells in blood and secondary lymphatic organs, the pig is an attractive model to study these cells, especially their combined features of the innate and the adaptive immune system. Using a 5' RACE-like approach, we translated a human/murine NGS library preparation strategy to capture full-length V-(D)-J TRG and TRD clonotypes in swine. After oligo(dT) primed conversion of input RNA, the cDNA population was enriched for full-length V(D)J TCR transcripts with porcine-specific primers including Illumina adaptor sequences as overhangs for Illumina MiSeq analysis. After quality control and processing by FastQC and ea-utils, porcine TRG and TRD sequences were mapped against the human IMGT reference directory. Porcine blood-derived CD2+ and CD2‾ TCR-γδ+ cells exhibited two distinct clonotypes Vγ11JγP1 (74.6%) and Vγ10JγP1 (57.7%), respectively. Despite the high TCR-δ diversity among CD2+ cells (39 clonotypes), both subsets shared the same abundant Vδ1DδxJδ4 clonotype at approximately identically frequencies (CD2+: 31.2%; CD2‾: 37.0%). The flexible nature of this approach will facilitate the assessment of organ-specific phenotypes of γδ T cell subsets alongside with their respective TCR diversity at single cell resolution.

Keywords: Next generation sequencing; Sus scrofa; TCR profiling; TRD; TRG; γδ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • CD2 Antigens / metabolism
  • Cells, Cultured
  • Endopeptidases / metabolism
  • Gene Expression Profiling
  • Genetic Variation
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunity, Innate
  • Mice
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Sequence Analysis, RNA / methods*
  • Swine / immunology*
  • T-Lymphocytes / physiology*

Substances

  • CD2 Antigens
  • Receptors, Antigen, T-Cell, gamma-delta
  • Endopeptidases
  • prenylated peptide-specific endoprotease