Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance

Nat Commun. 2017 Mar 1:8:14760. doi: 10.1038/ncomms14760.

Abstract

γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm relates to human Vδ2neg T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time. Contrastingly, Vδ2+ T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vδ1+ T cells have therefore evolved a distinct biology from the Vδ2+ subset, involving a central, personalized role for the γδ TCR in directing a highly adaptive yet unconventional form of immune surveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • CX3C Chemokine Receptor 1 / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Clone Cells / cytology*
  • Complementarity Determining Regions / genetics
  • Cytotoxicity, Immunologic
  • Genetic Variation
  • Humans
  • Immunologic Surveillance*
  • Interleukin-15 / pharmacology
  • Phenotype
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Tissue Donors
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism

Substances

  • Biomarkers
  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • Complementarity Determining Regions
  • Interleukin-15
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tumor Necrosis Factor Receptor Superfamily, Member 7