The Gaus Group research focuses on developing new super-resolution fluorescence microscopes and analysis routines to understand the decision-making processes of T cells. Single molecule data provide a unique ‘bottom up’ perspective to T cell signalling networks in intact and live cells. With new analysis strategies, they can map where signalling begins and how signals spread through the cells. They also use nanotechnology to control where and when T cells are stimulated.
T cells can distinguish between peptides derived from damaged and infected cells such as cancer cells, and benign ‘self’ peptides derived from healthy cells. The T cell receptor binds to peptides bound to major histocompatibility complexes, so-called peptide-MHC (pMHC) complexes, on the surface of antigen presenting cells. Despite the relatively weak T cell receptor-pMHC binding affinity, T cells can sense and respond to even a single antigenic peptide. This can lead to effector functions including secretion of potent mediators and killing of infected or cancerous cells. However, there are many more self peptides than foreign peptides presented to T cells and in this case, the correct decision for the T cell is to do nothing at all.
Despite extensive experimental and mathematical work, we do not understand how pMHC recognition by the T cell receptor initiates intracellular signalling and how the signalling network processes information ultimately leading to T cell fate decisions. This is a central question in peptide-mediated immunity and vaccine development and could help us to identify new avenues for drug design to combat autoimmune diseases and agents for cancer immunotherapy.
“With new single molecule tools, and our formidable team, the only limit to what we can achieve is our imagination,” says Kat.
- How does a T cell distinguish between peptides derived from “self” and “non-self”?
- How does a single antigen recognition event lead to T cell activation?
- Which antigen recognition event leads to immunological memory?
- How do mechanical forces influence T cell receptor signalling?