: The functional avidity of a CD8+ T cell correlates with the magnitude of its effector function. High avidity are more effective than low avidity CD8+ T cells in clearing virus in vivo. Antigen density is one factor that controls avidity, however it is likely that other factors are involved in the determination of avidity. The goal of these studies is to determine the role of CD4+ T helper cells in the generation of a high avidity CD8+ T cells following intranasal immunization of mice with the paramyxovirus simian virus 5. In this model, the number of high avidity CD8+ T cells is severely reduced in CD4-depleted mice, suggesting that CD4+ T cell """"""""help"""""""" provided by CD40/CD40L-mediated APC activation and/or cytokine secretion influence CD8+ T cell avidity. The role of APC activation in the generation of CD8+ T cell avidity will be determined in mice deficient for CD40. The role of T helper cytokines in the generation of high avidity CD8+ T cells will be determined by identifying candidate cytokines and analyzing cytokine receptor expression on CD8+ T cells. The necessity and sufficiency of the candidate cytokine for high avidity CD8+ T cell responses will also be assessed. These studies will determine whether APC-derived signals and/or cytokines promote the activation, survival or expansion of high avidity CD8+ T cells. Knowledge of the factors that control the functional avidity may lead to more efficacious vaccines that elicit high avidity CD8+ T cell responses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI054093-03
Application #
6921504
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Prograis, Lawrence J
Project Start
2003-05-16
Project End
2006-05-15
Budget Start
2005-05-16
Budget End
2006-05-15
Support Year
3
Fiscal Year
2005
Total Cost
$53,492
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157