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Mechanisms Of Autoantigen Cleavage During Cell Death, Xiwei Wu

Loma Linda University Electronic Theses, Dissertations & Projects

Specific intracellular autoantigens targeted by autoantibodies in systemic autoimmune and chronic inflammatory diseases undergo posttranslational modifications, such as cleavage, during cell death that could potentially enhance their immunogenicity. In light of the increasing interest in the immunological consequences of defective clearance of apoptotic cells, we explored whether autoantigens cleaved during apoptosis undergo an additional wave of proteolysis as apoptosis progresses to secondary necrosis in the absence of phagocytosis. Jurkat T cells treated with different apoptosis inducers underwent a rapid apoptosis that gradually progressed to secondary necrosis. During the initial apoptotic stages, several nuclear autoantigens, including PARP, Topo I, and LEDGF/p75 …