INSIGHTS INTO CD8 T CELL-MEDIATED PATHOLOGY DURING EXPERIMENTAL CEREBRAL MALARIA

Abstract

Cerebral malaria is a fulminant complication in severe malaria infections that is responsible for the wide majority of deaths in malaria. In the mouse model, CD8 T cells play a pathogenic role in experimental cerebral malaria (ECM), but the epitopes they recognize remains unknown. In my PhD project, a PbA cDNA library enriched in open reading frames was constructed, expressed in EL4 cells and screened against T reporter cell lines bearing TCRs from CD8 T cells sequestered in the brains of mice during ECM. Two novel epitopes were discovered this way. Functional malaria-specific CD8 T cells accumulate in the brains, where cross-presentation of cognate epitopes occur in the cells lining blood-brain barrier (BBB) during ECM. Further experiments indicate that CD8 T cells of multiple malaria specificities synergistically damage BBB in the brains, suggesting inhibition of cross-presentation might have therapeutic potential in cerebral malaria.