University of Oxford - Sciences
The stoichiometry of the CD4/Lck complex in T cells
T cells form a central part of the human immune system, patrolling the body for potential signs of danger.
Our immune cells are developed in a manner that makes them exquisitely sensitive to the tiniest amounts of antigen without overreacting to ourselves; a failure to do this results in autoimmune disease or cancer. My project was focused on expanding our understanding of the ability of T cells to discriminate between self and non-self with such a high sensitivity and accuracy.
The T cell receptor (TCR) is a surface molecule that allows T cells to dock with and interrogate other cells in your body for signs of danger. Activation of the T cell occurs when the TCR recognises danger and recruits activatory molecules to itself such as the kinase called Lck. A recent model for T cell discrimination suggests that the delay taken to recruit Lck forms part of the discrimination machinery that sensitises the cell to correct signals. This delay is caused by having few molecules of Lck bound to the CD4 co-receptor. Over the course of the summer I used a range of techniques to investigate the CD4-Lck interaction both in isolated protein samples and in live cells. Through co-immunoprecipitations performed in mouse T cells and fluorescence correlation spectroscopy performed on human T cells we were able to show that there were always abundant amounts of Lck associated with CD4. This suggested that the delay in recruiting Lck to the TCR is not a rate-limiting step in activating our immune system, and that other mechanisms must be at play.
The leadership training provided me with a valuable insight into the dynamics of teamwork and people-management. I was surprised to discover that the training week led by Maurice came in handy several times during the summer when discussing the management of projects or leading small meetings. In a high-pressure lab environment everyone has their own projects and priorities, and I found it incredibly useful to bring people together in a way that allows the sharing of resources, expertise and advice.
My Laidlaw placement further developed my interest in biomedical research at Oxford in a way that my undergraduate degree had given me a taste of. By working alongside PhD students and postdoctoral scientists I learned a great deal about undertaking research at a world-leading institution and that was a big factor in my decision to pursue research at a postgraduate level. It also allowed me to develop interpersonal and management skills in areas I didn’t even know I was interested in. These are skills I am grateful to have going forward with cutting-edge research. I am now starting a DPhil in Infection, Immunology and Translation Medicine at the Medical Sciences Doctoral Training Centre in Oxford and I hope to continue a career in basic biological research that has translational aspects for tangibly improving human health.