Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Plasmactyoid dendritic cells (pDC) of the innate immune system are important mediators of antiviral immunity through their ability to produce large amounts of type I interferons (IFNs) - antiviral cytokines upon viral infection. This function of pDC has been linked to the expression of Toll-like receptors 7 and 9 (TLR 7, 9), which are pathogen recognition receptors that sense viral nucleic acids. In mice, pDC are uniquely characterized by high-level expression of Ly49Q, a protein receptor specific for MHC I molecules, another set of protein receptors present on all nucleated cells. Ly49Q recognition of MHC I has been previously found by our lab. The current objective is to investigate the implications of Ly49Q:MHC I interaction in pDC function and antiviral immunity. To investigate the influence of Ly49Q:MHC-I interactions on pDC antiviral function, type I IFN secretion by pDC in response to viruses will be measured both in vitro and in vivo using Ly49Q gene deficient mice. The mechanism underlying Ly49Q modulation of cytokine secretion by pDC will also be determined. The functions of pDC receptors are important research questions with broad implications. Dysfunctional pDC activity in patients has resulted in documented cases of increased viral susceptibility and reduced immune functions in humans. The human functional analogues to the mouse Ly49s are the Killer Immunoglobulin Receptors. However, due to the extreme polymorphism in human individuals, questions regarding the functions of pDC receptors are better studied in inbred laboratory mouse models. Insight into human pDC immune response against pathogens and pathogen infected cells can be acquired from characterizing the Ly49Q ligand and receptor interaction in the mouse model.