The ultimate goal of these studies is to understand how exposing the skin of mice to ultraviolet radiation (UVR) leads to the production of suppressor T lymphocytes that inhibit the rejection of UVR-induced skin cancers. Specifically, we wish to define the cellular and molecular events that lead to suppression of immune responses in UV-irradiated mice. In the second competing renewal of this project, we propose to use lymphocytes from T cell receptor transgenic mice that express a clonotypic alpha beta T cell receptor specific for peptide 111 - 119 of influenza hemagglutinating antigen and the anti-clonotypic antibody 6.5 to follow the fate and activity of T cells in response to immunization in order to determine how this pathway is altered by UV irradiation of the host and whether T effector and suppressor cells arise from the same clonotypic T cell population. Second, we will continue our studies characterizing immune responses affected by the two pathways of UV-induced systemic immune suppression, one mediated by DNA damage the other by cis-urocanic acid. Third, we will further analyze the role of DNA damage in UV-induced alterations of cutaneous antigen-presenting cells. Approaches include using DNA repair deficient XPC knockout mice to increase DNA damage, and liposomes containing photolyases specific for UV photoproducts as a means of removing DNA damage. We will begin to define the mechanism(s) by which lesions in DNA inhibit APC function.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA052457-11
Application #
6172167
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Finerty, John F
Project Start
1990-07-01
Project End
2000-11-30
Budget Start
2000-05-01
Budget End
2000-11-30
Support Year
11
Fiscal Year
2000
Total Cost
$8,220
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Microbiology/Immun/Virology
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
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