Unravelling the CTLA-4 immune checkpoint: from cell biology to clinical application

Our immune system acts like an army with powerful weapons which are used to fight off invading microbes like bacteria and viruses. However, in a number of diseases such as arthritis and diabetes, T cells in our immune system attack our own bodies, as if the weapon has been fired at the wrong target. Normally, special immune cells called Treg (regulatory T cells) prevent this from happening. Tregs carry a protein called CTLA-4 which hoovers up and destroys the signals that tell T cells to fire. Changes to hoovering efficiency can be critical and auto immune disease can develop when these cells do not work properly.

Despite being essential to our health, we know surprisingly little about how the CTLA-4 system works. In this study we will generate detailed new knowledge on how CTLA-4 behaves in different settings. This will allow us to understand precisely what happens when it goes wrong and will enable us to design and apply better treatments for diseases that affect a large number of people.