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Functional Phenotypes of Human Vγ9Vδ2 T Cells in Lymphoid Stress Surveillance

GammaDelta Therapeutics Ltd., The Westworks, 195 Wood Lane, London W12 7FQ, UK
Peter Gorer Department of Immunobiology, Kings College, London SE1 9RT, UK
Immunotherapy Unit, Department of Urology, Medical University of Innsbruck, 6020 Innsbruck, Austria
Authors to whom correspondence should be addressed.
Cells 2020, 9(3), 772;
Received: 14 February 2020 / Revised: 16 March 2020 / Accepted: 19 March 2020 / Published: 22 March 2020
Butyrophilin and butyrophilin-like proteins select γδ T cells and direct the migration of γδ T cell subsets to distinct anatomical sites. γδ T cells expressing Vδ2 paired with Vγ9 (Vγ9Vδ2 T cells) are the predominant γδ T cell type in human peripheral blood. Vγ9Vδ2 T cells, which cannot be studied easily in vivo because they do not exist in rodents, are often referred to as innate-like T cells. The genetically recombined γδ T cell receptor (TCR) that responds to isoprenoid-derived pyrophosphates (phosphoantigens) produced by infected and malignant cells in a butyrophilin-dependent manner qualifies them as therapeutically relevant components of the adaptive immune system. On the other hand, cell-surface proteins such as the C-type lectin CD161 mark a functional phenotype of Vγ9Vδ2 T cells that mediates TCR-independent innate-like responses. Moreover, CD56 (neural cell adhesion molecule, NCAM) and the G protein-coupled receptor GPR56 define Vγ9Vδ2 T cells with increased cytolytic potential and, like CD161, may also be expressed by dendritic cells, principally facilitating the generation of an innate-like immunological synapse. In this review, we summarise current knowledge of Vγ9Vδ2 T cell functional phenotypes that are critical to lymphoid stress surveillance. View Full-Text
Keywords: Vγ9Vδ2 T cells; butyrophilin; CD161; CD56; GPR56 Vγ9Vδ2 T cells; butyrophilin; CD161; CD56; GPR56
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Nussbaumer, O.; Thurnher, M. Functional Phenotypes of Human Vγ9Vδ2 T Cells in Lymphoid Stress Surveillance. Cells 2020, 9, 772.

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