Oreste Acuto

Molecular mechanisms of T cell activation and differentiation

We are interested in understanding how T cells, central actors of adaptive immune responses, become activated when they encounter foreign substances. Dissecting the molecular underpinning of this process may lead to the discovery new and more effective ways to diagnose, prevent and heal immune dysfunction that leads to autoimmunity or susceptibility to infection.

A T cell (right) being activated, with a B cell (left).

Defining the T cell receptor signalosome by mass spectrometry.

Towards this goal, we study the nature of signals received by T cells during activation and how these signals are chemically decoded to drive complex decisions. Signalling then leads to immediate or sustained cell responses and determines cell fate. We employ state-of-the-art quantitative mass spectrometry-based proteomics and integrate this approach with in vitro and in vivo genetic and pharmacological manipulation of cells. We integrate this knowledge using computational modeling of signaling circuits and molecular structures, to understand the complex signals involved in T cell regulation.

Relevant Publications

Howden A.J.M, , Geoghegan V., Katsch K. , Efstathiou G., Bhushan B., Boutureira O., Thomas B., Trudgian D. C., Kessler B. M., Dieterich D. C., Davis B. G., O. Acuto
2013

Nature Methods 10: 343-346.

Paster W., Brockmeyer C. , Fu, G., Simister, P.C., de Wet, B., Martinez-Riaño A., Hoerter J. A. H. Feller S.M., Wuelfing C., Gascoigne N. R. J., Acuto O
2013

J. Immunol 190: 3749-3756.

Fu, G., Casas, J., Rigaud, S., Rybakin, V., Lambolez, F., Brzostek, J. Hoerter, J.A.H., Paster, W., Acuto, O., Cheroutre, H., Sauer, K., and N. R.J. Gascoigne
2013

Nature 504: 441-5.

Nika K., Soldani C., Salek M., Paster W., Gray A., Etzensperger R., Fugger L. Polzella P., Cerundolo V., Omer Dushek O., Höfer T.  Viola A. and O. Acuto
2010

Immunity 32: 66-777.

oreste.acuto@path.ox.ac.uk

Research Areas