Grant: Master's Award: Canada Graduate Scholarships

The majority of the components that are needed for the vitamin D endocrine system are present within immune cells that normally defend the host against foreign pathogens. This suggests an important regulatory role for vitamin D during an immune response. The active form of vitamin D suppresses certain elements of the adaptive immune response while it induces other elements of the innate immune system. Cross-talk steps between the innate and adaptive systems, such as antigen presentation, allow for the induction of appropriate effector functions against infections. Antigen presentation is a key mechanism that controls the activation of the adaptive immune response. Naïve CD8+ T-cells can become activated or "primed" to become effector cells, such as virus specific killer Tcells (CD8+ cytotoxic T-cells or CTLs,)when they recognize peptide- major histocompatibility complex class-I (MHC-I) complexes presented by professional antigen presenting cells (pAPCs). A recently defined antigen presentation pathway is cross-presentation, which allows for the delivery of exogenously derived antigens to MHC-I molecules. Several studies have reported on the immune effects of vitamin D, however there is no information on its effects on cross-presentation. There is some evidence indicating that vitamin D affects key cells, such as pAPCs, that contribute to cross-presentation. Vitamin D appears to suppress inflammation, and thus it could be concluded that crosspresentation occurring in the presence of vitamin D can be affected to induce an anti-inflammatory state. However, other evidence shows that vitamin D can enhance certain innate immune functions through indirect interactions with the toll like-receptor (TLR) pathways. Thus this project will examine such interactions to define how vitamin D can regulate cross-presentation in the absence or presence of certain TLR ligands.