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 and Benjamin E. Willcox ()
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Martin S. Davey: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham
Carrie R. Willcox: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham
Stephen P. Joyce: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham
Kristin Ladell: Cardiff University School of Medicine
Sofya A. Kasatskaya: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
James E. McLaren: Cardiff University School of Medicine
Stuart Hunter: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham
Mahboob Salim: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham
Fiyaz Mohammed: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham
David A. Price: Cardiff University School of Medicine
Dmitriy M. Chudakov: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Benjamin E. Willcox: Cancer Immunology and Immunotherapy Centre, Institute for Immunology and Immunotherapy, University of Birmingham

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14760

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