Research
T cells help orchestrate immune responses which rid the body of disease-causing agents such as viruses, bacteria and parasites. T cells have evolved to distinguish self (any cell in the body) from non-self (potential infectious agents).
T cells can recall a previous encounter with a particular invader (pathogen) and mount a faster and more vigorous response to subsequent encounters to the extent that the infection goes unnoticed. This is how resistance to particular strains of the flu develops and is also how vaccines have their protective effect.
However, in some cases T cells mistakenly recognise components of the different cells and organs in the body as infectious agents. This mistake can lead to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, juvenile diabetes, systemic lupus erythematosus and other devastating illnesses.
Much scientific research effort is therefore directed towards the goal of developing drugs that can suppress the immune system under circumstances where it is too active or where it turns against self rather than infectious agents. One approach is to interfere with the chemical signals that are generated inside the T cells upon recognition of foreign agents (or self, as the case may be).
The T cell receptor for antigen (TcR) recognises peptide fragments from the pathogen on the surface of cells that have been infected with or have engulfed (eaten) that agent. The peptide is displayed on their surface to alert the immune system to the presence of an invader. However, recognition of a peptide from the foreign invader is in itself insufficient to initiate most immune responses.
Specialised cells called antigen presenting cells (APCs) that have been exposed to the pathogen also express a protein called B7 on the cell surface which alerts the immune system by sending a second signal through CD28 on the T cell.
Both the TcR and CD28 activate phosphoinositide 3-kinases (PI3Ks), a family of enzymes used by B and T cells to generate signalling molecules which influence cell division, metabolism, motility and gene expression. We have previously identified one member of this family, called p110delta, which plays a particularly important role in the cells of the immune system, but which is dispensable for other cells in the body.
Drugs that inhibit the function of p110delta may therefore be used to dampen harmful immune responses. We are therefore continuing to investigate how exactly T cells respond if p110δ has been genetically inactivated in order to further validate this enzyme as a drug target. We are also investigating how the related PI3Ks, p110α, p110β and p110γ might also contribute to the regulation of immune responses. To answer these questions we use genetic approaches in conjunction with fluorescence-based technologies to monitor signalling pathways and to analyse immune responses.
Updated 23 August, 2011