Grant: $240,800 - National Institutes of Health - Sep. 23, 2009
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Award Description: The focus of the parent grant is to study the role of ?? T cells in the immune response to infection with Borrelia burgdorferi. Despite our knowledge of the existence of ?? T cells for 25 years, we still know very little regarding their contribution to the immune response, nor almost anything of their specificity. The parent grant proposed that Borrelia lipoproteins engage TLR2 on antigen presenting dendritic cells (DC), which then activate synovial ?? T cells in Lyme arthritis. In turn, the ?? T cells express very high levels of Fas-Ligand (FasL), which would perform two functions. First, they might kill Fas sensitive effector ?? T cells, and second, they might actually activate myeloid DC also via Fas, since DC express high levels of the Fas inhibitor, c-FLIP. What was missing from this model was what the actual antigen was that directly stimulated synovial V?1 cells. In addition, an in vivo murine model was needed to test the role of ?? T cells in systemic Borrelia infection. Studies to date have now produced the first human soluble T cell receptor (sTCR) for V?1 cells, and have also shown that mice lacking ?? T cells manifest greater Borrelia burden and increased carditis. This award proposes to extend these two important advances as progress has been more rapid than anticipated and funds are not available to pursue these directions at a competitive pace. These funds will be used to scale up production of the sTCR-?? to determine its specificity and to identify the ligand(s) using mass spectroscopy. The second part will allow us to adoptively transfer ?? T cells from mice lacking FasL or IFN? to determine whether these known effector molecules in ?? T cells confers protection.
Project Description: See award description above
Infrastructure Description: n/a
Jobs Summary: n/a (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 23, 2009. Help expand these official descriptions using the wiki below.