Systems approach to the analysis of T cell receptor signal transduction

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T cells are white blood cells that continuously patrol the body in search of evidence of infection or cancer. Recognition by T cells occurs when receptors on the T cell surface directly bind to fragments or 'antigens' derived from infectious organisms or cancer cells. This recognition is particularly important because T cells, in addition to themselves killing infected or cancerous cells, also coordinate and control other elements of the immune response that are required to remove these threats. T cell antigen recognition is the key to understanding appropriate and helpful immune responses to dangerous antigens (e.g. from harmful bacteria) as well as inappropriate, unhelpful responses to innocuous or self-antigens, which results in allergic and autoimmune diseases, respectively. Although the T cell antigen receptor (TCR) is clearly very important it is still unclear how binding of the TCR to antigen leads to the activation of the T cell and how the TCR detects the rare dangerous antigens amongst the far more numerous harmless antigens. This study aims to address these questions using a systems medicine based approach combining mathematical modelling and range of experimental techniques. An improved understanding of T cell antigen recognition will enhance our ability to manipulate the immune response in order to improve vaccines, treat autoimmune and allergic diseases, and prevent rejection of organ transplants.