Research Projects

Research in our lab uses a combination of cellular and molecular approaches in the analysis of T-cell responses to bacterial pathogens. Many virulence factors have been identified that allow bacteria to survive and replicate within the mammalian host. Our research focuses on the immune consequences of these survival strategies, particularly the recognition of bacterial infection by CD8+ T-cells.

When foreign protein antigens are introduced into the cytosol of host cells, the antigens are processed and assembled onto host molecules encoded by the class I major histocompatibility complex (MHC-I). These peptide/MHC-I complexes are displayed on the cell surface and can be recognized by CD8+ T-cells. The CD8+ T-cells employ a variety of immune mechanisms in an attempt to effect clearance of the pathogen. These functions include direct lysis of the infected presenting cell, secretion of cytokines that initiate an inflammatory response, and expansion of the responding CD8+ T-cell clones for amplification of the effector responses and generation of immune memory.

Specifically, we are interested in the types of bacterial-host cell interactions that result in the introduction of bacterial proteins into the cytosol of host cells. Although bacterial pathogens can be divided into the categories based on their subcellular localization, bacteria that are not localized to the cytoplasm of host cells often have evolved mechanisms to introduce a subset of their proteins into the cytosol. We are interested in using the response of CD8+ T-cells to reveal these antigens so that we can study their role in bacterial pathogenesis. We are equally interested in defining the precise mechanisms by which the host responds to these antigens to provide protective immunity.