Human gamma delta T cells: Evolution and ligand recognition

Cell Immunol. 2015 Jul;296(1):31-40. doi: 10.1016/j.cellimm.2015.04.008. Epub 2015 May 6.


The γδ T cell lineage in humans remains much of an enigma due to the low number of defined antigens, the non-canonical ways in which these cells respond to their environment and difficulty in tracking this population in vivo. In this review, we survey a comparative evolutionary analysis of the primate V, D and J gene segments and contrast these findings with recent progress in defining antigen recognition by different populations of γδ T cells in humans. Signatures of both purifying and diversifying selection at the Vδ and Vγ gene loci are placed into context of Vδ1+ γδ T cell recognition of CD1d presenting different lipids, and Vγ 9Vδ2 T cell modulation by pyrophosphate-based phosphoantigens through the butyrophilins BTN3A. From this comparison, it is clear that co-evolution between γδ TCRs and these ligands is likely occurring, but the diversity inherent in these recombined receptors is an important feature in ligand surveillance.

Keywords: B30.2; Butyrophilin; CD1d; Phosphoantigens; T cell receptor; T cells; Vdelta1; Vgamma9Vdelta2.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antigens, CD1d / immunology
  • Butyrophilins
  • Callithrix
  • Diphosphates / immunology
  • Evolution, Molecular*
  • Humans
  • Ligands
  • Lymphocyte Activation / immunology*
  • Membrane Glycoproteins / immunology
  • Pan troglodytes
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocytes / immunology*


  • Antigens, CD1d
  • BTNL9 protein, human
  • Butyrophilins
  • CD1D protein, human
  • Diphosphates
  • Ligands
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell, gamma-delta