(taken from application) T-cells are likely to play a crucial role in inflammatory bowel disease (IBD) pathogenesis. Our focus has centered on the analysis of the T-cell receptor (TCR), the specific antigen recognition element of the T-cell, as a means to implicate T-cell responses to specific antigen(s) in disease pathogenesis and to potentially identify disease relevant T-cell clones. Our previous studies on TCR usage have clearly shown that a highly specific T-cell response is present in individuals with IBD and this response is characterized by persistent T-cell expansions which are shared by genetically related individuals. This directly implicates a response by T-cells in IBD affected individuals to conventional antigen(s). The major goals of this grant proposal are to further define the nature of these T-cell expansions in IBD and investigate for potential T-cell recognized antigen(s) relevant to IBD pathogenesis. Specifically, we plan to characterize: (1) the TCR usage of the IL-2 receptor positive subset of intestinal T-cells; (2) the TCR usage of the bile-duct associated T-cells in the clinically distinct subset of individuals with primary sclerosing cholangitis, and; (3) the relationship between major histocompatibility complex (MHC) and TCR usage in families with IBD. By utilizing this information on TCR usage, specific T-cell clones of interest, which express TCRs that are a part of a public or private motif, will be isolated and utilized in long-term, molecular and cellular based strategies. These strategies, which are based on rapidly emerging technologies, will aim to define the cognate antigen(s) of these potentially disease relevant T-cells, and thus allow further insight into the etiopathogenesis of IBD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08DK002532-01
Application #
2437845
Study Section
Special Emphasis Panel (SRC)
Program Officer
Podskalny, Judith M,
Project Start
1998-09-30
Project End
2003-09-29
Budget Start
1998-09-30
Budget End
1999-09-29
Support Year
1
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