title: Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance.
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 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.
authors.affiliation: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Davey
authors.affiliation: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Willcox
authors.affiliation: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Joyce
authors.affiliation: Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Kristin
authors.initials: K
authors.lastname: Ladell
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia.|Pirogov Russian National Research Medical University, Moscow 117997, Russia.|Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic.
authors.forename: Sofya A
authors.initials: SA
authors.lastname: Kasatskaya
authors.affiliation: Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: McLaren
authors.affiliation: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Hunter
authors.affiliation: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Mahboob
authors.initials: M
authors.lastname: Salim
authors.affiliation: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Fiyaz
authors.initials: F
authors.lastname: Mohammed
authors.affiliation: Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia.|Pirogov Russian National Research Medical University, Moscow 117997, Russia.|Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic.
authors.forename: Dmitriy M
authors.initials: DM
authors.lastname: Chudakov
authors.affiliation: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Willcox
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1 / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002999:Clone Cells / Q000166:cytology*; D022801:Complementarity Determining Regions / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D014644:Genetic Variation; D006801:Humans; D007157:Immunologic Surveillance; D019409:Interleukin-15 / Q000494:pharmacology; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D014019:Tissue Donors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D022801:Complementarity Determining Regions; D019409:Interleukin-15; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7