CD36 peptides that block cytoadherence define the CD36 binding region for Plasmodium falciparum-infected erythrocytes

Mature Plasmodium falciparum parasitized erythrocytes (PE) sequester from t he circulation by adhering to microvascular endothelial cells. PE sequestra tion contributes directly to the virulence and severe pathology of falcipar um malaria. The scavenger receptor, CD36, is a major host receptor for PE a dherence. PE adhesion to CD36 is mediated by the malarial variant antigen, P. falciparum erythrocyte membrane protein 1 (PfEMP1), and particularly by its cysteine-rich interdomain region 1 (CIDR-1). Several peptides from the extended immunodominant domain of CD36 (residues 139-184), including CD36 1 39-155, CD36 145-171, CD36 146-164, and CD36 156-184 interfered with the CD 36-PfEMP1 interaction. Each of these peptides affected binding at the low m icromolar range in 2 independent assays. Two peptides, CD36 145-171 and CD3 6 156-184, specifically blocked PE adhesion to CD36 without affecting bindi ng to the host receptor intercellular adhesion molecule-1 (ICAM-1). Moreove r, an adhesion blocking peptide from the ICAM-1 sequence inhibits the PfEMP 1-ICAM-1 interaction without affecting adhesion to CD36, These results conf irm earlier observations that PfEMP1 is also a receptor for ICAM-1, Thus, t he region 139-184 and particularly the 146-164 or the 145-171 regions of CD 36 form the adhesion region for P. falciparum PE, Adherence blocking peptid es from this region may be useful for modeling the PE/PfEMP1 interaction wi th CD36 and for development of potential anti-adhesion therapeutics. (C) 19 99 by The American Society of Hematology.