Translational research is defined as research that uses findings from basic science studies for practical applications that enhance health and well-being both in humans and animals.

CD8 T-cells are important for protection against a plethora of different pathogens and are also capable of killing cancerous cells. In contrast, dysregulated CD8 T-cell immunity can have devastating effects, for example autoimmunity and graft rejection. Professor Linda Wooldridge leads the research aimed at understanding the basic immunology of the CD8 T-cell response and translate the groups’ findings to improve our understanding of the mechanisms that underlie CD8 T-cell mediated disease and the development of novel therapeutic strategies. As such, the group has active projects that span three different areas:

Understanding the basic mechanisms involved in CD8 T-cell activation

• CD8 T-cells recognize small peptide fragments complexed with Major Histocompatibility Complex Class I (pMHCI) molecules expressed at the target cell surface, binding via the T-cell receptor (TCR) and CD8 coreceptor. The CD8+ T cell activation involves two key interactions:
• The TCR/pMHCI interaction: determines antigen specificity. Promiscuity is a characteristic feature of this interaction and it is essential for effective immunity.
• The pMHCI/CD8 interaction: has a potent ability to tune the antigen specific immune response by a number of different mechanisms. The CD8 coreceptor can enhance antigen sensitivity by up to 1 million fold!

We are interesting in understanding both of these interactions and how to manipulate them for therapeutic benefit.

Understanding the pathogenesis of common CD8 T-cell mediated disease

Currently we have several active projects in this area which include:

• Understanding the role of CD8 T-cells in the pathogenesis of neuro-inflammatory diseases in humans and animals. In particular, we are interested in investigating the possibility that these conditions are triggered by an invading pathogen.
• Understanding the requirements for effective immunity against viral infections in human and animals such as HIV and FIV.
• Defining the pathogenic triggers of T-cell leukaemia.
• Studying the molecular/biochemical basis of alloreactivity.

Translation for the development of novel therapeutic strategies

We are interesting in developing therapies in the following areas of unmet need:

• T-cell therapy for cancer: The identification of strategies that can be used to generate large numbers of T-cells for therapy. In addition, we are examining the possibility that the CD8 coreceptor could be used as way of engineering T-cells with increased sensitivity to cancer antigens and the ability to kill cancer cells more effectively. 
• Novel therapeutics to use in autoimmunity: We are investigating the use of agents that target the CD8 coreceptor to block unwanted autoreactive T-cell activation in autoimmune diseases such as Type I Diabetes (TID) and Multiple Sclerosis (MS).

Please feel free to get in touch with Professor Linda Wooldridge if you are interested in any of these research areas.