Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: A receptor for human placental infection

Malaria during the first pregnancy causes a high rate of fetal and neonatal death. The decreasing susceptibility during subsequent pregnancies correla tes with acquisition of antibodies that block binding of infected red cells to chondroitin sulfate A (CSA), a receptor for parasites in the placenta. Here we identify a domain within a particular Plasmodium falciparum erythro cyte membrane protein 1 that binds CSA, We cloned a var gene expressed in C SA-binding parasitized red blood cells (PRBCs). The gene had eight receptor -like domains, each of which was expressed on the surface of Chinese hamste r ovary cells and was tested for CSA binding. CSA linked to biotin used as a probe demonstrated that two Duffy-binding-like (DBL) domains (DBL3 and DB U) bound CSA. DBL7, but not DBU, also bound chondroitin sulfate C (CSC) lin ked to biotin. a negatively charged sugar that does not support PRBC adhesi on. Furthermore, CSA, but not CSC, blocked the interaction with DBL3 both C SA and CSC blocked binding to DBL7. Thus, only the DBL3 domain displays the same binding specificity as PRBCs. Because protective antibodies present a fter pregnancy block binding to CSA of parasites from different path of the world, DBL-3, although variant, may induce cross-reactive immunity that wi ll protect pregnant women and their fetuses.