Antigen Presentation In Induction of an Anti-Viral CD8+ T Cell Response


CD8+ T cells are a major component of the cellular response to viral infection. These cells generally recognize peptides derived from viral proteins in complex with host MHC Class I molecules. The major focus of my laboratory is to elucidate the mechanism by which these peptides are generated in a natural viral infection. Knowledge of the pathways of presentation of these peptides will allow the rational design anti-viral and anti-tumor vaccines allowing generation of CD8+ T cells responses via more natural, and therefore more efficient, pathways.


To this end we are investigating which cells must present antigen in vivo for efficient activation of CD8+ T cells. The localization and timing of peptide presentation, as well as the properties of the antigen-presenting cell are all areas under current investigation in a number of viral systems. Other questions include whether these cells must be infected for efficient generation of peptides recognized by CD8+ T cells, and how the requirements differ between the same antigens encoded in different viruses.


The Effects of Psychological Stress Upon Antigen Presentation and Dendritic Cell Function


In a collaboration with Drs Emmy Truckenmiller and Robert Bonneau we investigate the effects of stress hormones, such as corticosterone (cortisol), upon both antigen presentation and dendritic cell (DC) phenotype and function in vitro and in vivo. Stress is immunosuppressive and the CD8+ T cell response to viral infection is dramatically reduced in stressed individuals. DC are cells that are likely vital for the induction of CD8+ T cell responses, so information about their phenotype under stressed conditions, as well as the efficiency of antigen presentation, will provide significant information for the treatment of many pathologies that are worsened with stress.


The Activation of Retinal Microglia in the Progression of Diabetic Retinopathy.


As part of the Juvenile Diabetes Research Foundation Diabetic Retinopathy Center at Penn State College of Medicine we are investigating the role of the resident immune cell population of the retina in the progression of Diabetic Retinopathy (DR). DR is a pathology that involves leakage of blood vessels, formation of new blood vessels, and death of the neuronal cells that pass information to the brain that is eventually interpreted as sight. A large number of individuals with diabetes will eventually progress to some level of diabetic retinopathy and some will lose their sight. Progression to diabetic retinopathy is strongly associated with an inflammatory response. Microglia are the resident macrophage population of the retina and so represent the likely source of inflammatory mediator such as cytokines, lipid mediators and reactive oxygen or nitrogen species that can cause vascular leakage and neuronal cell death. We are investigating the heterogeneity of microglia, their production of proinflammatory mediators and their interactions with neurons that can cause their activation.