Glycophorin B is the erythrocyte receptor of <i>Plasmodium falciparum</i> erythrocyte-binding ligand, EBL-1

Abstract

In the war against Plasmodium, humans have evolved to eliminate or modify proteins on the erythrocyte surface that serve as receptors for parasite invasion, such as the Duffy blood group, a receptor for Plasmodium vivax, and the Gerbich-negative modification of glycophorin C for Plasmodium falciparum. In turn, the parasite counters with expansion and diversification of ligand families. The high degree of polymorphism in glycophorin B found in malaria-endemic regions suggests that it also may be a receptor for Plasmodium, but, to date, none has been identified. We provide evidence from erythrocyte-binding that glycophorin B is a receptor for the P. falciparum protein EBL-1, a member of the Duffy-binding-like erythrocyte-binding protein (DBL-EBP) receptor family. The erythrocyte-binding domain, region 2 of EBL-1, expressed on CHO-K1 cells, bound glycophorin B(+) but not glycophorin B-null erythrocytes. In addition, glycophorin B(+) but not glycophorin B-null erythrocytes adsorbed native EBL-1 from the P. falciparum culture supernatants. Interestingly, the Efe pygmies of the Ituri forest in the Democratic Republic of the Congo have the highest gene frequency of glycophorin B-null in the world, raising the possibility that the DBL-EBP family may have expanded in response to the high frequency of glycophorin B-null in the population.