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

V delta 2(+) T cells form the predominant human gamma delta T-cell population in peripheral blood and mediate T-cell receptor (TCR)-dependent anti-microbial and anti-tumour immunity. Here we show that the V delta 2(+) compartment comprises both innate-like and adaptive subsets. V gamma 9(+) V delta 2(+) T cells display semi-invariant TCR repertoires, featuring public V gamma 9 TCR sequences equivalent in cord and adult blood. By contrast, we also identify a separate, V gamma 9(-) V delta 2(+) T-cell subset that typically has a CD27(hi)CCR7(+)CD28(+)IL-7R alpha(+) 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 V gamma 9(-) V delta 2(+) T cells featuring dominant clonal expansions and an effector phenotype. These findings redefine human delta d T-cell subsets by delineating the V delta 2(+) T-cell compartment into innate-like (V gamma 9(+)) and adaptive (V gamma 9(-)) subsets, which have distinct functions in microbial immunosurveillance.