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 ORCID: https://orcid.org/0000-0002-9856-2938, Kasatskaya, Sofya A., McLaren, James E. ORCID: https://orcid.org/0000-0002-7021-5934, Hunter, Stuart, Salim, Mahboob, Mohammed, Fiyaz, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, 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:	Publication
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:	16 Nov 2024 05:00
URI:	https://orca.cardiff.ac.uk/id/eprint/100895

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