A clonotypic Vγ4Jγ1/Vδ5Dδ2Jδ1 innate γδ T-cell population restricted to the CCR6⁺CD27⁻ subset

Nat Commun. 2015 Mar 13:6:6477. doi: 10.1038/ncomms7477.

Abstract

Here we investigate the TCR repertoire of mouse Vγ4(+) γδ T cells in correlation with their developmental origin and homeostasis. By deep sequencing we identify a high frequency of straight Vδ5Dδ2Jδ1 germline rearrangements without P- and N-nucleotides within the otherwise highly diverse Trd repertoire of Vγ4(+) cells. This sequence is infrequent in CCR6(-)CD27(+) cells, but abundant among CCR6(+)CD27(-) γδ T cells. Using an inducible Rag1 knock-in mouse model, we show that γδ T cells generated in the adult thymus rarely contain this germline-rearranged Vδ5Dδ2Jδ1 sequence, confirming its fetal origin. Single-cell analysis and deep sequencing of the Trg locus reveal a dominant CDR3 junctional motif that completes the TCR repertoire of invariant Vγ4(+)Vδ5(+) cells. In conclusion, this study identifies an innate subset of fetal thymus-derived γδ T cells with an invariant Vγ4(+)Vδ5(+) TCR that is restricted to the CCR6(+)CD27(-) subset of γδ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Movement
  • Germ-Line Mutation
  • Green Fluorescent Proteins / metabolism
  • Immunity, Innate
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Phenotype
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, CCR6 / metabolism*
  • Sequence Analysis, DNA
  • Single-Cell Analysis
  • T-Lymphocyte Subsets / cytology*
  • Thymus Gland / metabolism
  • Tissue Distribution
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism*

Substances

  • CCR6 protein, mouse
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, CCR6
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Green Fluorescent Proteins