Previous studies by this group has shown that a component of the capsular polysaccharide of Bacteroides fragilis, known as PS A, is a potent T cell mitogen and it is involved in the production of abscess. The proposed studies will examine the structural features of PS A that affect its ability to stimulate T cell proliferation. They will examine the structural attributes of PS A that controls T cell activation and the ability of PS A to bind to cell surfaces. The second part of the study will characterize the cells responding to PS A by phenotype, by response to repeated stimulation, within the T cell repertoire, and the cytokine profile. The third part of the study will define the antigen-presenting cells and binding proteins. This work will involve characterizing the """"""""feeder cell"""""""" requirements, definition of the cell type which is important for stimulating response, and assessment of polysaccharide binding to cells. Additional studies will characterize the cell molecules important T cell stimulation and will use blocking antibody and """"""""knock-out"""""""" mice. One of the ultimate goals of this investigation is to understand how polysaccharides activate T cells, which might in turn lead to the design of the interventional strategies for potential new vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI039576-02
Application #
2672727
Study Section
Special Emphasis Panel (ZRG5-BM-1 (02))
Project Start
1997-05-01
Project End
2002-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Sen, Jayita; Liu, Xueqiao; Roller, Richard et al. (2013) Herpes simplex virus US3 tegument protein inhibits Toll-like receptor 2 signaling at or before TRAF6 ubiquitination. Virology 439:65-73
Duan, Jinyou; Kasper, Dennis L (2011) Oxidative depolymerization of polysaccharides by reactive oxygen/nitrogen species. Glycobiology 21:401-9
Murawski, Matthew R; McGinnes, Lori W; Finberg, Robert W et al. (2010) Newcastle disease virus-like particles containing respiratory syncytial virus G protein induced protection in BALB/c mice, with no evidence of immunopathology. J Virol 84:1110-23
Duan, Jinyou; Chung, Hachung; Troy, Erin et al. (2010) Microbial colonization drives expansion of IL-1 receptor 1-expressing and IL-17-producing gamma/delta T cells. Cell Host Microbe 7:140-50
van Lint, Allison L; Murawski, Matthew R; Goodbody, Rory E et al. (2010) Herpes simplex virus immediate-early ICP0 protein inhibits Toll-like receptor 2-dependent inflammatory responses and NF-kappaB signaling. J Virol 84:10802-11
Troy, Erin B; Kasper, Dennis L (2010) Beneficial effects of Bacteroides fragilis polysaccharides on the immune system. Front Biosci (Landmark Ed) 15:25-34
Dasgupta, Suryasarathi; Kasper, Dennis L (2010) Novel tools for modulating immune responses in the host-polysaccharides from the capsule of commensal bacteria. Adv Immunol 106:61-91
Velez, Christopher D; Lewis, Colleen J; Kasper, Dennis L et al. (2009) Type I Streptococcus pneumoniae carbohydrate utilizes a nitric oxide and MHC II-dependent pathway for antigen presentation. Immunology 127:73-82
Duan, Jinyou; Avci, Fikri Y; Kasper, Dennis L (2008) Microbial carbohydrate depolymerization by antigen-presenting cells: deamination prior to presentation by the MHCII pathway. Proc Natl Acad Sci U S A 105:5183-8
Mazmanian, Sarkis K; Round, June L; Kasper, Dennis L (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620-5

Showing the most recent 10 out of 19 publications