Relationship between Plasmodium falciparum protein structure and inhibitory signal induction of immune cells

The deadliest malaria strain for humans is Plasmodium falciparum. We examined the Repetitive Interspersed Family (RIFIN) protein expressed on the 0222700 gene of P. falciparum. RIFIN first attaches to the surface of a red blood cell (iRBC), then binds to immunoreceptors in cytotoxic T (CT) immune cells. This induces inhibitory signals to the CT cell, thereby allowing the parasite to evade the immune system. We seek to understand this mechanism of immune evasion to better battle malaria and identify which structural modifications prevent the parasite from inhibiting the immune system. RIFIN was genetically modified with targeted sites of DNA polymerase to delete the region of RIFIN which enters the cytosol of the iRBC. These modified proteins were then transfected into P. falciparum-infected red blood cells. To measure if RIFIN had properly migrated from the nucleus of the transgenic parasite to the surface of the iRBC, we introduced the transgenic parasites to KIR2DL1 immunoreceptor and APC proteins, which would fluoresce if signal induction occurred. Our results did not show any statistically significant APC expression. We conclude that the cytosolic region of RIFIN is likely necessary for proper migration from the nucleus of the transgenic parasite to the surface of the iRBC, therefore necessary for later signal induction to immune cells.