T CELL RECOGNITION ANTIGENS IN SYMPTOMATIC HUMAN CAROTID

U.S. National Inst/Neuro/Ds/Stroke, Bethesda MD

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Abstract

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.