The human Vδ2 T-cell compartment comprises distinct innate-like Vγ9 and adaptive Vγ9 subsets.

Vδ2 T cells form the predominant human γδ T-cell population in peripheral blood and mediate T-cell receptor (TCR)-dependent anti-microbial and anti-tumour immunity. Here we show that the Vδ2 compartment comprises both innate-like and adaptive subsets. Vγ9 Vδ2 T cells display semi-invariant TCR repertoires, featuring public Vγ9 TCR sequences equivalent in cord and adult blood. By contrast, we also identify a separate, Vγ9 Vδ2 T-cell subset that typically has a CD27CCR7CD28IL-7Rα naive-like phenotype and a diverse TCR repertoire, however in response to viral infection, undergoes clonal expansion and differentiation to a CD27CD45RACXCR1granzymeA/B effector phenotype. Consistent with a function in solid tissue immunosurveillance, we detect human intrahepatic Vγ9 Vδ2 T cells featuring dominant clonal expansions and an effector phenotype. These findings redefine human γδ T-cell subsets by delineating the Vδ2 T-cell compartment into innate-like (Vγ9) and adaptive (Vγ9) subsets, which have distinct functions in microbial immunosurveillance.