Some pulmonary pathogens, such as gammaherpesviruses and m. tuberculosis are able to escape immune control and persist for prolonged periods of time in the host. However, we have very little understanding of how persisting antigen affects the immune response or the mechanisms by which these pathogens escape immune control.
To begin to address these issues we are focusing on two models of persistent infection.
First, we are collaborating with Dr. Marcy Blackman (Trudeau Institute) to determine the impact of persistent antigen presentation on the quality of T cell memory in a mouse model of gammaherpesvirus infection. Current studies are directed at identifying antigens expressed during lytic and latent stages of virus infection with a view to understanding the role of T cells specific for these epitopes in maintaining latency.
Second, we are collaborating with Dr. Gary Winslow (Wadsworth Center, Albany, NY) to study immunity to m. tuberculosis, a bacterial pathogen that establishes a persistent infection the lung. Our primary goal at this time is to generate tools to investigate the immune response to this infection in detail. In this regard, we have generated TCR transgenic mice specific for the ESAT-6/Ab epitope to study the induction of T cell responses to infection.
We have also generated T cell hybridomas specific for various tuberculosis epitopes, including ESAT-6/Ab, and a tetramer that specifically identifies ESAT-6/Ab-specific T cells.