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

作者：Martin S. Davey, Carrie R. Willcox, Stephen Paul Joyce, Kristin Ladell, Sofya A. Kasatskaya, James E. McLaren, Stuart Hunter, Mahboob Salim, Fiyaz Mohammed, David A. Price, Dmitriy M. Chudakov, Benjamin E. Willcox · 发表于：Nature Communications · 年份：2017 · DOI：10.1038/ncomms14760 · 被引用次数：294 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

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 Vδ2 neg 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.