Choosing the Microbiology and immunology program at Wake Forest has been one of the best decisions I have made in my desire to learn more about events taking place at the cell level that ultimately help the body succumb to or fight disease. This is made especially possible by a department with a lot of collaborative research ongoing through the coming together of experienced scientists from the fields of bacteriology, virology and most important to me immunology. With an awesome learning environment and a veritable sense of dedication to the needs of every student, I could not have been anywhere else!

Research

An important component of the cell‐mediated immune system is the cytotoxic T lymphocyte (CTL). CTL are involved in clearing intracellular pathogens by recognizing antigenic peptides presented in the context of MHC class I molecules, which leads to lysis of the infected cell as well as the secretion of cytokines. It is clear from previous studies that not all CTL are equally effective for pathogen clearance. A critical parameter that determines in vivo efficacy is avidity, i.e. the sensitivity of a CTL to pMHC. CTL of high avidity are far superior to lower avidity cells for reducing viral burden. Whilst a high avidity CD8+ T‐cell response is always desirous in vivo, there is little understanding regarding its generation. It is well established that the amount of pMHC presented by an antigen presenting cell (APC) in vitro directs the avidity of the CTL, with low pMHC resulting in generation of high avidity CTL and high pMHC resulting in the generation of low avidity CTL. However these studies have always been performed using non‐professional APC as stimulators. In contrast, work from our laboratory has shown that bone marrow derived dendritic cells (BMDCs), the most efficient professional APC, generate high avidity CTL regardless of the amount of pMHC presented. Generation of high functional avidity is independent of the extent of TCR engagement of pMHC as peptide‐pulsed non‐professional APC and BMDC induce similar levels of TCR internalization on naïve T cells. My project work will focus on understanding the molecular mechanism by which dendritic cells prime high avidity CD8+ T‐cell responses independent of the level of pMHC. This will involve an examination of the recruitment of molecules that play a role in T‐cell priming, e.g. costimulatory as well as signalling molecules, to the immunological synapse. In addition the role of DC produced soluble factors that are in many cases required for optimal T‐cell activation will be investigated by employing a transwell system. Finally, time lapse microscopy will be used to test the hypothesis that the generation of high avidity CTL by DC presenting high levels of pMHC is controlled by the length of time that T cells are in conjugate with this APC. Ultimately, understanding how high avidity CTL are generated may help inform vaccine development as well as treatment of chronic diseases.