How do gamma delta T cells recognise target cells?

Hands holding test tube and pipette

New research from the University of Birmingham’s Institute of Immunology and Immunotherapy has found how an important class of immune cells, gamma delta T cells (γδ T cells), is able to recognise target cells.

Recently published in Immunity in collaboration with Thomas Herrmann from the University of Würzburg, the study focussed on the most prevalent γδ T cells in the blood, which are able to recognise signs of infection or cancer in target cells.

They do this by sensing the presence of small molecules, phosphoantigens, inside the target cells. When exposed to these molecules, which can be increased in target cells that are infected or cancerous, the γδ T cells become powerfully activated and can then kill the target cells and produce immune activation molecules.

The mechanism underpinning this had been unclear, but this vital study identifies a key protein called Butyrophilin-2A1 (BTN2A1) on the target cell that is recognised by a critical receptor on γδ T cells, the T cell receptor (TCR).

This BTN2A1 molecule works together with a second related molecule present on the target cells, BTN3A1, which acts as a direct sensor for phosphoantigens, to sensitize target cells for TCR recognition.

Joint lead author, Dr Carrie Willcox, from the Institute of Immunology and Immunotherapy, commented: “This type of γδ T cell is the one most commonly focussed on in attempts to harness γδ T cells for immunotherapy against cancer. Understanding how they recognise signs of abnormality in targets cells could help speed up these developments.”

Senior author, Professor Ben Willcox, from the Institute of Immunology and Immunotherapy, said: “With funding from the Wellcome Trust, this study provides a new molecular model for how recognition takes place. In doing so, it opens up further research into other novel molecules that may be involved, which will likely be relevant to both infection and cancer recognition. Building on our research in this area, our lab is also developing new drugs in order to exploit this pathway for cancer therapy.”