T cell receptor signalling in γδ cell development: strength isn't everything

gamma delta cells have been conserved across similar to 450 million years of evolution, from which they share the distinction, alongside alpha beta T cells and B cells, of forming antigen receptors by somatic gene recombination. However, much about these cells remains unclear. Indeed, although gamma delta cells display 'innate-like' characteristics exemplified by rapid tissue-localised responses to stress-associated stimuli, their huge capacity for T cell receptor (TCR)gamma delta diversity also suggests 'adaptive-like' potential. Clarity requires a better understanding of TCR gamma delta itself, not only through identification of TCR ligands, but also by correlating thymic TCR gamma delta signalling with commitment to gamma delta effector fates. Here, we propose that thymic TCR gamma delta-ligand engagement versus ligand-independent signalling differentially imprints innate-like versus adaptive-like characteristics on developing gamma delta cells, which fundamentally dictate their peripheral effector properties.