Human gamma delta T cells: Evolution and ligand recognition

The gamma delta 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 gamma delta T cells in humans. Signatures of both purifying and diversifying selection at the V delta and V gamma gene loci are placed into context of V delta 1+ gamma delta T cell recognition of CD1d presenting different lipids, and V gamma 9V delta 2 T cell modulation by pyrophosphate-based phosphoantigens through the butyrophilins BTN3A. From this comparison, it is clear that co-evolution between gamma delta TCRs and these ligands is likely occurring, but the diversity inherent in these recombined receptors is an important feature in ligand surveillance. (C) 2015 Elsevier Inc. All rights reserved.