Bacteria that can survive and replicate within mammalian cells are sequestered from many of the body’s immune defense mechanisms. To clear an infection with an intracellular pathogen, the effector functions of CD8 + T cells (also known as cytotoxic T lymphocytes or CTL) must be activated. CD8 + T cells are alerted to the presence of intracellular bacteria via specific recognition of bacterial antigens displayed on the infected cell surface by class I major histocompatibility complex (MHC-I) molecules. In the mouse, three well-characterized MHC molecules (K, D, and L, now collectively known as the MHC-Ia molecules) have been shown to bind and present bacterial antigens to CD8 + T cells during infection. However, the mouse MHC locus contains at least 30 other genes that encode proteins with predicted similarities to MHC-Ia. The function of most of these proteins (collectively referred to as MHC-Ib proteins) is not well understood.

I recently developed a MHC-Ia deficient mouse model of systemic infection and used this model to show that MHC-Ib restricted CD8 + T cells alone are sufficient to protect mice against challenge with Listeria monocytogenes. L. monocytogenes is a gram-positive intracellular bacterium that has been used for decades as a model organism to study both the manipulation of host cell processes by bacteria and the host response to infection. Listeria species can be genetically manipulated and the mouse model of systemic infection is highly reproducible. Thus this model serves as an excellent system to study the interaction of intracellular bacteria with their host cells.

Current work in my lab is focused on 1) determining which MHC-Ib molecules are involved in presentation of bacterial antigens to CD8 + T cells and 2) identifying and characterizing the nature of the dominant and subdominant bacterial antigens that are displayed on the cell surface during Listeria infection. It is often true that dominant antigens are derived from essential bacterial components, therefore, another focus in the lab is to determine whether candidate antigens have any role in the pathogenesis of L. monocytogenes infection. The results of these studies will have significant implications for the design of effective vaccines against a variety of intracellular bacterial pathogens including organisms such as Mycobacterium tuberculosis and Chlamydia trachomatis.