C lonal selection in the human Vd1 T cell repertoire indicates ?d TCR-dependent adaptive immune surveillance

?d T cells are considered innate-like lymphocytes that rapidly respond to stress without clonal selection and differentiation. We used next generation sequencing approaches to probe how this paradigm related to human Vd2- ?d T cells, implicated in responses to viral infection and cancer. The prevalent Vd1 TCR repertoire is private and initially unfocussed in cord blood, typically becoming strongly focussed on a few high-frequency clonotypes by adulthood. Clonal expansions differentiate from a naïve to effector phenotype associated with CD27 downregulation, retain proliferative capacity and T cell receptor (TCR) sensitivity, display increased cytotoxic markers and altered homing capabilities, and are relatively stable over time. Contrastingly, Vd2+ T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vd1+ T cells have therefore evolved a different biology from the Vd2+ subset, involving a central, personalised role for the ?d TCR in directing a highly adaptive form of immune surveillance.