Omer Dushek

Molecular immunology of T cell surface receptors

T cells are white blood cells that initiate immune responses that can clear infections and cancers. The decision to respond is made by the integration of signals from a large number of different T cell surface receptors using many intracellular signalling molecules. We use a diverse set of quantitative methods to uncover the mechanisms underlying signal integration and exploit this new information to improve human health.

The main focus of our research has been to understand how the immune system discriminates between normal and abnormal (e.g. infected) tissues. This job has been delegated to specialised white blood cells called T-cells. These cells patrol the body continuously scanning the surfaces of other cells for protein fragments called antigens. When their T cell antigen receptors (TCRs) bind to even a single foreign-derived antigen (e.g. a fragment from a virus) they initiate immune responses. Their TCR can also bind to highly abundant self-derived antigens (e.g. fragments of our normal proteins) with slightly lower affinity. How do T cells avoid activation when their TCR bind abundant self-antigens, yet respond when they bind even a single foreign-antigen? This is the foundational question underlying our research.

The decision to respond is made by the complicated signalling machinery that integrates signals from the TCR and a host of other, accessory, receptors on the T cell surface.

We use a combination of quantitative experiments and mathematical modelling to uncover the operational and molecular mechanisms underlying signal integration by T cell surface receptors.

A subset of the general paradigms that we work on:
-How T cells discriminate self vs. non-self foreign or neoantigen pMHC (e.g. here).
-How T cells achieve high antigen sensitivity able to respond to even a single pMHC (e.g. here).
-How T cells integrate signals from a host of accessory receptors (e.g. here).
-How T cell activation is achieved by synthetic antigen receptors (e.g. here).
-How the molecular reach of T cell surface receptors and their enzymes impact signalling (e.g. here).
-How T cells implement kinetic proofreading at a molecular level (e.g. here)

Group members

  • Omer Dushek (Group leader)
  • Kirtana Sivasubramanian (PhD student)
  • Jesús Siller Farfán (Postdoc)
  • Alina Shomuradova (PhD student)
  • Ashna Patel (PhD student)
  • Mikhail Kutuzov (Postdoc)
  • Jordan Kramer (PhD student)
  • Anna Huhn (PhD student)
  • Jose Cabezas Caballero (PhD student)
  • Sofia Bustamante Eguiguren (PhD student)

Latest news