Dept. of Microbiology and Immunobiology
Harvard Medical School
NRB, Room 852 A
77 Avenue Louis Pasteur
Boston, MA 02115
Click here to visit the Starnbach Lab Website.
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.
Bernstein-Hanley, I, Coers, J, Balsara, ZR, Taylor, GA, Starnbach, MN, Dietrich, WF. The p47 GTPases IGTP and Irgb10 map to the Chlamydia trachomatis susceptibility locus Ctrq-3 and mediate cellular resistance in mouse. Proceedings of the National Academy of Sciences, USA, 2006, 103(38):14092-14097.
D’Orazio, SEF, Shaw,CA, Starnbach, MN. H2-M3 restricted CD8+ T cells are not required for MHC class Ib restricted immunity against Listeria monocytogenes, Journal of Experimental Medicine, 2006, 203:383-391. (pdf)
van der Velden, AW, Copass, MK, and Starnbach, MN. Salmonella inhibit T cell proliferation through a direct, contact-dependent immunosuppressive effect. Proceedings of the National Academy of Sciences, USA, 2005, 102:17769-17774. (pdf)
Loomis WP, Starnbach MN. T cell responses to Chlamydia trachomatis. Current Opinion in Microbiology 2002;5:87-91
Fling SP, Sutherland RA, Steele LN, Hess B, D'Orazio SE, Maisonneuve J, Lampe MF, Probst P, Starnbach MN. CD8+ T cells recognize an inclusion membrane-associated protein from the vacuolar pathogen Chlamydia trachomatis. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1160-5.
Ballard JD, Collier RJ, Starnbach MN. Anthrax toxin-mediated delivery of a cytotoxic T-cell epitope in vivo. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12531-4.