Immature, double negative thymocytes commit themselves for maturation to the double positive phenotype by recombining the PCR beta chain locus and inducing the expression of TCR beta protein. PF inhibits the differentiation of double negative cells into double positive thymocytes.
In specific aim 1, the investigator will first identify the stage of the double negative cells and the status of the T cell receptor beta chain locus after the treatment of the cell by PF. If the recombination of the beta chain locus is absent or reduced, the investigator will consider the control of the recombination and transcription of TCR beta locus as a critical event that is affected by the drug PF. If the recombination of the beta chain locus is absent or reduced, the investigator will consider this event as the target for the action of PF. He will then attempt to identify the transcription factors that are required for recombination of the beta chain locus and whose expression/activity is inhibited by PF. If the TCR beta chain locus recombination is unaffected, the investigator will use an appropriate transgenic mouse strain that expresses an already arranged beta chain gene in an attempt to identify the PF mediated molecular block in the development of double positive thymocytes. In the second specific aim, the investigators will examine the expression of Rel transcription factor family members after the treatment of the antigen specific T cell clone with cognate antigen and PF. They will examine the expression and the DNA binding activities of these proteins to determine whether or not the expression or the activity of these proteins is affected by PF.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW000982-02
Application #
6078393
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Michels, Kathleen M
Project Start
1998-09-30
Project End
2001-09-29
Budget Start
1999-09-30
Budget End
2000-09-29
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Brandeis University
Department
Type
Organized Research Units
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454