Overview for non-biologists
The immune system protects us from all sorts of infectious agents. The importance of this type of protection unfortunately becomes all too apparent in AIDS patients whose immune systems are destroyed by the human immunodeficiency virus. On the other hand, inappropriate immune responses have also long been known to be the cause of great suffering in patients with, for example, asthma, rheumatoid arthritis and diabetes. Understanding how the immune system works in detail is therefore very important as it has tremendous potential for reducing human suffering.
These are particularly exciting times for this type of research because the recent advent of the Human Genome Project means that we can now think about identifying all the elements of complicated biological systems such as T-cells. Whilst initially increasing the complexity of the task, in the longer term it will be much easier to be certain that we are doing the right thing when we need to boost the immune response or to switch it off when things are going wrong.
We already know that the immune system is controlled by a complex mixture of proteins, some of which are secreted by white blood cells and others that are present on their surfaces. We and others are particularly interested in how the cell surface proteins work because their presence on cells in the blood makes them such good, well-exposed immunotherapeutic targets. Our recent analyses of the pool of genes expressed by white blood cells (i.e. their “transcriptome”) indicates, somewhat unexpectedly, that even though, overall, large numbers of immune genes remain to be discovered, we may have identified all of the most important ones encoding proteins that are expressed on the surfaces of these cells. This has shifted the emphasis of our work toward understanding the functions of these proteins.
In order to understand how these proteins work, we rely heavily on producing highly ordered crystals of the proteins that allow us to determine their detailed structures. This provides insights into how proteins and cells recognize one and another and how we might go about blocking the proteins’ functions. In other work we are beginning to use so-called “single-molecule” methods that allow us to track the behaviour of individual proteins. Our long-term goal is to integrate these ideas and findings into predictive theories of how white blood cells behave, such as the “kinetic-segregation” model, which attempts to describe how the inside of a white blood cell “learns” that it needs to respond to specific contacts made with other cells. Our hope is that such models will provide a reliable framework for manipulating human immune responses in a therapeutic setting.