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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 CD27 hi CCR7 + CD28 + IL-7Rα +  naive-like phenotype and a diverse TCR repertoire, however in response to viral infection, undergoes clonal expansion and differentiation to a CD27 lo CD45RA + CX 3 CR1 + granzymeA/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.

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