Michael N. Starnbach
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 which 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 antigens by CD8+ T-cells. CD8+ T-cell recognition of an infected cell results in both the lysis of the infected cell and secretion of cytokines which activate other immune mechanisms. Some of the pathogens we are using as models are Chlamydia trachomatis, Salmonella typhimurium, Shigella flexneri, and Bacillus anthracis.
One group of projects in the lab is directed at understanding the role of CD8+ T-cells in immunity to the obligate intracellular pathogen C. trachomatis. We have been able to raise CD8+ T-cell lines from Chlamydia infected mice and show that these lines are specific for Chlamydia infected cells in vitro. Upon adoptive transfer of these CD8+ T-cells into Chlamydia infected mice, a reduction in bacterial load can be measured in the spleen. Our current research on C. trachomatis is directed at identifying the Chlamydia antigens which are recognized by CD8+ T-cells as well as dissecting the mechanism by which Chlamydia antigens are processed for recognition. The goal of this continuing research effort is to better understand acquired immunity to pathogens of this genus which are a prevalent cause of sexually transmitted disease worldwide, and a major cause of blindness in developing countries.
Another project involves the use of anthrax toxin to deliver CD8+ T-cell epitopes into the cytoplasm of host cells. Introduction of these epitopes into the cytoplasm allows for their processing and presentation on MHC class I molecules to CD8+ T-cells. We have designed recombinant toxins which are devoid of toxic activity and express epitopes from various bacterial and viral pathogens. When injected into mice these fusion proteins prime a CD8+ T-cell response against the pathogen. In addition, mice immunized with these fusion proteins are protected against subsequent challenge with the pathogen. We are in the process of constructing anthrax toxin fusions which contain epitopes from a variety of bacteria, viruses, and tumors. These studies may lead to the development of anthrax toxin-based anti-bacterial, anti-viral, and anti-tumor therapies and vaccines.
NRB Building, Room 852
77 Ave. Louis Pasteur
Boston, MA 02115