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 CD27hiCCR7+CD28+IL-7Rα+ naive-like phenotype and a diverse TCR repertoire, however in response to viral infection, undergoes clonal expansion and differentiation to a CD27loCD45RA+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.

Cancer Immunology and Immunotherapy Centre Institute of Immunology and Immunotherapy University of Birmingham Birmingham B15 2TT UK

Central European Institute of Technology Masaryk University Brno 625 00 Czech Republic

Centre for Data Intensive Biomedicine and Biotechnology Skolkovo Institute of Science and Technology Moscow 143026 Russia

Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease Institute of Immunology and Immunotherapy University of Birmingham Birmingham B15 2TT UK

Department of Experimental Immunology Academic Medical Center Amsterdam 1105 AZ The Netherlands

Pirogov Russian National Research Medical University Moscow 117997 Russia

Renal Transplant Unit Division of Internal Medicine Academic Medical Center Amsterdam 1105 AZ The Netherlands

Shemyakin Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science Moscow 117997 Russia

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