Cell adhesion interactions are important in the understanding of various cellular processes where specific recognition of proteín surfaces is required. Erythrocytes parasitized (PE)by P. Falciparum segregate/sequester themselves, from the circulation by adhering to microvascular endothelial cells (MEC). This segregation contributes directly to the virulence and severe pathology of malaria derived from P. falciparum; it is known that cell surface protein CD36 is an important host receptor for PE adherence, and this adhesion is mediated by the malarial variant antigen, P. falciparum erythrocyte membrane protein 1 (PfEMP1) and also by its cysteine-rich interdomain region 1 (CIDR-1). A group of peptides from the immunodominant domain of CD36 (residues 139-184) ranging in sizes from 17 to 29 amino acids, interfered with the CD36-PfEMP1 protein-protein interaction. All these peptides diminished binding at low micromolar range. Two such peptides, CD36 145-171 and CD36 156-184, selectively blocked PE adhesion to CD36 with no effect on its binding to the host receptor intercellular adhesion molecule-1 (ICAM-1).
It is also described that an adhesion blocking peptide from the ICAM-1 sequence interferes with PfEMP1– ICAM-1 interaction with no effect on its adhesion to CD36. These experiments validate earlier evidence that PfEMP1 is also a receptor for ICAM.
In summary it is shown that region 139-184 ,comprise the binding/adhesion for P. falciparum. These peptides can be be very useful for understanding the PE/PfEMP1 interaction with CD36 and for possible development of anti-adhesion molecular therapies.