T cells are specialised white blood cells that protect us from infections and cancer by recognising abnormal cells. A remarkable feature of these cells is their ability to distinguish between the body’s own healthy tissues and even tiny amounts of foreign material. Understanding how T cells make this decision is the central question driving our research.
The integrated signal from many surface receptors determines T cell responses.
T cells (red) interacting with antigen presenting cells (green).
T cells continuously scan other cells for protein fragments (antigens) using their T cell antigen receptors (TCRs). They can become activated after recognising just a single foreign-derived antigen, yet normally remain unresponsive to the many closely related self-antigens found throughout the body. How T cells achieve this extraordinary sensitivity while maintaining self-tolerance remains one of the fundamental questions in immunology.
Our research investigates how signals from the TCR and a network of co-signalling receptors are integrated by intracellular signalling pathways to control T cell activation. We develop quantitative experimental and computational approaches to measure and model these signalling processes, uncovering the molecular mechanisms that govern cellular decision-making. By understanding how T cells integrate information at immune cell interfaces, we aim to inform the design of next-generation immunotherapies for cancer, infectious disease, and autoimmunity.
2026
Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors
Caballero-Cabezas, J., Huhn, A., Kutuzov, M.A., Andre, V., Shomuradova, A., Peeters, B.W.A., Gillespie, G.M., van der Merwe, P.A., Dushek, O.
Nature Biomedical Engineering – Apr;10(4):753-764
2025
The molecular reach of antibodies crucially underpins their viral neutralisation capacity
Huhn, A., Nissley, D., Wilson, D.B., Kutuzov, M., Donat, R., Tan, T.K., Zhang, Y., Barton, M.I., Liu, C., Dejnirattisai, W., Supasa, P., Mongkolsapaya, J., Townsend, A., James, W., Screaton, G., van der Merwe, P.A., Deane, C.M., Isaacson, S.A., Dushek, O.
Nature Communications – Jan 2;16(1):338
2024
Using CombiCells, a platform enabling titration and combinatorial display of cell surface ligands, to study T cell antigen sensitivity by TCRs, CARs, and BiTEs
Patel, A., Andre, V., Eguiguren, S.B., Barton, M.I., Denham, E.M., Pettmann, J., Morch, A.M., Kutuzov, M.A., Siller-Farfan, J.A., Dustin, M.L., van der Merwe, P.A., Dushek, O.
The EMBO Journal – Jan;43(1):132-150
2023
Inefficient exploitation of accessory receptors reduces the sensitivity of chimeric antigen receptors.
Burton,J., Siller-Farfan, J.A., Pettmann, J., Salzer, B., Kutuzov, M., van der Merwe, P.A. and Dushek, O.
Proc Natl Acad Sci USA. – 20(2): e2216352120.
2022
Mechanical forces impair antigen discrimination by reducing differences in T cell receptor off-rates.
Pettmann, J., Awada, L., Bartosz, R., Huhn, A., Faour, S., Kutuzov, M., Limozin, L., Weikl, T.R., van der Merwe, P.A., Robert, P. and Dushek, O.
EMBO J. – 42(7): e111841.
2021
The discriminatory power of the T cell receptor.
*Pettmann, J., *Huhn, A., *Abu Shah, E., Kutuzov, M.A., Wilson, D.B., Dustin, M.L., Davis, S.J., van der Merwe, P.A. and Dushek, O.
eLife – 10: e67092.
2014
Phenotypic models of T cell activation.
Lever, M., Maini, P.K., van der Merwe, P.A. and Dushek, O.
Nature Reviews Immunology – 14(9): 619-29.
2012
Non-catalytic tyrosine-phosphorylated receptors.
Dushek, O., Goyette, J. and van der Merwe, P.A.
Immunological Reviews – 250(1): 258-76.
Dunn School projects available for this year’s UNIQplus programme
January 2026
The UNIQplus programme is aimed at supporting talented undergraduates from under-represented groups, who would find continuing into postgraduate study a challenge for reasons other than their academic ability, to consider postgraduate study.
Rewiring T cell co-receptors to improve the safety of cancer immunotherapy
January 2026
A new study from the Dushek and van der Merwe labs demonstrates a novel strategy to reduce dangerous off-target effects in engineered T cell therapies.
Jose Cabezas-Caballero awarded prestigious Physiological Society Prize
June 2025
The award recognises Jose’s research on T cell engineering, as well as his ability to engage a wide audience on the therapeutic potentials of this work.
New advances towards optimising the antigen sensitivity of CAR-T cells
January 2025
A new paper by the group of Omer Dushek makes important advances towards improving CAR-T technology.