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

Davey, Martin S., Willcox, Carrie R., Joyce, Stephen P., Ladell, Kristin, Kasatskaya, Sofya A., McLaren, James E., Hunter, Stuart, Salim, Mahboob, Mohammed, Fiyaz, Price, David A., Chudakov, Dmitriy M. and Willcox, Benjamin E. 2017. Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance. Nature Communications 8 , 14760. 10.1038/ncomms14760

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Additional Information: This work is licensed under a Creative Commons Attribution 4.0 International License.
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 26 May 2017
Date of Acceptance: 30 January 2016
Last Modified: 02 Jun 2020 13:30
URI: http://orca-mwe.cf.ac.uk/id/eprint/100895

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