The C-terminal segment of the Cysteine-rich inter-domain of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1) determines CD36 binding and elicits antibodies that inhibit adhesion of parasite-infected erythrocytes

School of Biological Sciences, Nanyang Technological University, 60, Nanyang Drive, Singapore 637551; AFMB, CNRS UMR6098 Marseille, France

^* To whom correspondence should be addressed. Email: julien{at}ntu.edu.sg. prpreiser{at}ntu.edu.sg.

	Abstract

Attachment of erythrocytes infected by Plasmodium falciparum to receptors of the micro-vasculature is a major contributor of pathology and morbidity associated with malaria. Adhesion is mediated by the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP-1), which is expressed at the surface of infected erythrocytes and is linked to both antigenic variation and cyto-adherence. PfEMP-1 contains multiple adhesive modules, including the Duffy binding-like domain and the cysteine-rich inter-domain region (CIDR). The interaction between CIDR and CD36 promotes stable adherence of parasitized erythrocytes to endothelial cells. Here we show that a segment within the C-terminal region of CIDR determines CD36 binding specificity. Antibodies raised against this segment can specifically block the adhesion to CD36 of erythrocytes infected with various parasite strains. Thus, small regions of PfEMP-1 that determine binding specificity could form suitable components of an anti-sequestration malaria vaccine effective against different parasite strains.