H2-M3 RESTRICTED T CELL RESPONSES
Principal Investigator: ERIC G contact PAMER
Abstract: DESCRIPTION: (Adapted from the Investigator's abstract): MHC class Ib molecules are members of a diverse family of non-polymorphic proteins that present bacterial peptides to cytolytic T lymphocytes (CTL). The murine H2-M3 molecule is an MHC class Ib molecule that binds short, hydrophobic peptides that contain N-formyl methionine at the amino terminus. Murine infection with Listeria monocytogenes, an intracellular bacterium, elicits CTL that recognize bacterial N-formylated peptides complexed with the H2-M3 MHC class Ib molecule. To enable direct identification of H2-M3 restricted T cells during bacterial infection, tetrameric H2-M3 molecules were complexed with one of the N-formylated L. monocytogenes peptides. These studies demonstrated that H2-M3 restricted T cell responses following primary infection occur more rapidly than H2-KDa restricted T cell responses. H2-M3 restricted T cells are cytolytic and secrete gamma-interferon, suggesting they play an important role in bacterial clearance. Interestingly, H2-M3 restricted memory T cell responses are attenuated compared to H2-KDa restricted responses. The specific aims of this application are: 1) To characterize H2-M3 restricted CTL responses in liver and gut of orally infected mice, providing insights into the role of MHC class Ib restricted T cells responses at a mucosal site following the natural route of L. monocytogenes infection; 2) To determine the mechanisms responsible for accelerated H2-M3 restricted T cell responses during primary infection with L. monocytogenes; and 3) To investigate the basis for attenuated H2-M3 restricted memory T cell responses in mice reinfected with L. monocytogenes. The studies proposed in this application will provide an unprecedented view of MHC class Ib restricted T cell responses to bacterial infection and will test the hypotheses that H2-M3 restricted T cells play a prominent role in intestinal immunity and that intestinal bacterial flora can influence pathogen specific T cell repertoires. Additionally, these experiments may provide novel insights into the factors driving in vivo T cell expansion and memory generation.
Funding Period: 2000-08-15 - 2006-05-31
more information: NIH RePORT
- Cross-recognition of N-formylmethionine peptides is a general characteristic of H2-M3-restricted CD8+ T cellsAlexander Ploss
Infectious Diseases Service, Department of Medicine and Laboratory of Antimicrobial Immunity, Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
Infect Immun 73:4423-6. 2005..We deleted the nonredundant fMIVTLF epitope and found that Listeria monocytogenes still primed fMIVTLF-specific T cells. Thus, cross-reactivity appears to be a more general characteristic of H2-M3-restricted T cells...
- Distinct regulation of H2-M3-restricted memory T cell responses in lymph node and spleenAlexander Ploss
Infectious Diseases Service, Department of Medicine and Laboratory of Antimicrobial Immunity, Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
J Immunol 175:5998-6005. 2005..These results may have important implications for prime-boost vaccination strategies...