Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance

Martin S. Davey, Carrie R. Willcox, Stephen P. Joyce, Kristin Ladell, Sofya A. Kasatskaya, James E. McLaren, Stuart Hunter, Mahboob Salim, Fiyaz Mohammed, David A. Price, Dmitriy M. Chudakov, Benjamin E. Willcox

Research output: Contribution to journalArticlepeer-review

140 Citations (Scopus)

Abstract

γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm relates to human Vδ2neg T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time. Contrastingly, Vδ2+ T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vδ1+ T cells have therefore evolved a distinct biology from the Vδ2+ subset, involving a central, personalized role for the γδ TCR in directing a highly adaptive yet unconventional form of immune surveillance.

Original languageEnglish
Article number14760
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 1 Mar 2017
Externally publishedYes

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