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 CD27^hiCCR7⁺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^loCD45RA⁺CX₃CR1⁺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.