MALARIA PEPTIDES EXPRESSED ON THE SURFACE OF INFECTED HEPATOCYTES - ISOLATION, SYNTHESIS AND FUNCTIONAL-ANALYSIS

It is now clear, from the results of various experiments, that the mal arial epitopes expressed on the surface of infected hepatocytes are th e target of at least two effector mechanisms: (1) a cytotoxicity, rest ricted by the major histocompatibility complex (MHC), which involves C D8(+) and CD4(+) T cells: and (2) antibody-dependent, cellular cytotox icity. Until now, Plasmodium epitopes have been characterized from kno wn parasite proteins and it appeared important to identify 'natural' p eptides. Epitopes have been investigated using two procedures for acid extraction, one for pools of livers from infected mice (P. yoelii) or cultures (P. vivax) and one for MHC-class-I molecules present in the plasma membranes of infected livers (P. yoelii), followed by fractiona tion using reversed-phase, high-performance, liquid chromatography (HP LC). Two new assays to estimate the potential interest of each newly i solated epitope have been developed in parallel: (1) a quantitative, H PLC-based assay of PCR products, to estimate the hepatic load of the p arasite; and (2) a brefeldin-A assay to check whether a peptide is pre sented on the membrane of the hepatocyte. The results of in-vivo and i n-vitro experiments indicate that some of the isolated peptides are th e targets of cytotoxic T cells.