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

• DOI: 10.1038/ncomms14760
• Publication Date: 2017-03-01T16:36:20Z
• Authors: 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
• Keywords: Adult; Cytotoxicity, Immunologic; Interleukin-15; 0303 health sciences; Science; Q; CX3C Chemokine Receptor 1; Genetic Variation; Cell Differentiation; Receptors, Antigen, T-Cell, gamma-delta; Complementarity Determining Regions; Article; Tissue Donors; Clone Cells; Tumor Necrosis Factor Receptor Superfamily, Member 7; 3. Good health; 03 medical and health sciences; Phenotype; Humans; Immunologic Surveillance; Biomarkers; Cell Proliferation

Abstractγδ 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 Vδ2negT 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.