There is increasing g evidence that inflammatory processes play an important role in the activation of carotid atherosclerotic plaque. We hypothesize T cell activation is central to the symptomatic activation of carotid atherosclerotic plaque. The presence of activated T cells and extensive expression of HLA molecules as well as proinflamatory cytokines are indicative of a local immunological activation in the atherosclerotic plaque, but antigens involved in this process have not yet been identified. Also it is unknown which group of clonal T cells populations are common for symptomatic plaques but are not identifiable as dominant or even existing populations in the asymptomatic ones. The goal of the present study is to identify peptide sequences that activate T cell populations isolated from symptomatic atherosclerotic plaque in order to reveal potential exogenous antigens or autoantigens that cause carotid plaque destabilization. T cell clones common for symptomatic carotid plaques will be identified using single-strand confirmation polymorphism technique. Antigenic sequences activating T cells will be identified with positional scanning by using soluble peptide combinatorial libraries. Knowledge of antigens or autoantigens involved in the activation of T cell clones will provide insight into the molecular and cellular mechanisms that generate carotid plaque destablilization and its conversion into the symptomatic state.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
International Research Fellowships (FIC) (F05)
Project #
5F05TW005469-02
Application #
6194467
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Sina, Barbara J
Project Start
2000-08-01
Project End
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
2
Fiscal Year
2000
Total Cost
$35,544
Indirect Cost
Name
U.S. National Institute/Neuro/Ds/Stroke
Department
Type
DUNS #
176819332
City
Bethesda
State
MD
Country
United States
Zip Code
20892
Shamsuzzaman, Abu; Amin, Raouf S; van der Walt, Christelle et al. (2015) Daytime cardiac repolarization in patients with obstructive sleep apnea. Sleep Breath 19:1135-40
Shamsuzzaman, Abu; Ackerman, Michael J; Kuniyoshi, Fatima Sert et al. (2014) Sympathetic nerve activity and simulated diving in healthy humans. Auton Neurosci 181:74-8
Shamsuzzaman, Abu; Amin, Raouf S; Calvin, Andrew D et al. (2014) Severity of obstructive sleep apnea is associated with elevated plasma fibrinogen in otherwise healthy patients. Sleep Breath 18:761-6
Nadareishvili, Z G; Koziol, D E; Szekely, B et al. (2001) Increased CD8(+) T cells associated with Chlamydia pneumoniae in symptomatic carotid plaque. Stroke 32:1966-72