VARIANT ANTIGENS AND ENDOTHELIAL RECEPTOR ADHESION IN PLASMODIUM-FALCIPARUM

Parasite-derived proteins expressed on the surface of erythrocytes inf ected with Plasmonium falciparum are important virulence factors, sinc e they mediate binding of infected cells to diverse receptors on vascu lar endothelium and are targets of a protective immune response, They are difficult to study because they undergo rapid clonal antigenic var iation in vitro, which precludes the derivation of phenotypically homo geneous cultures. Here we have utilized sequence-specific proteases to dissect the role of defined antigenic variants in binding to particul ar receptors. By selection of protease-resistant subpopulations of par asites on defined receptors we (i) confirm the high rate of antigenic variation in vitro; (ii) demonstrate that a single infected erythrocyt e can bind to intercellular adhesion molecule 1, CD36, and thrombospon din; (iii) show that binding to intercellular adhesion molecule 1 and CD36 are functions of the variant antigen; and (iv) suggest that bindi ng to thrombospondin may be mediated by other components of the infect ed erythrocyte surface.