Variant antigens and endothelial receptor adhesion in Plasmodium falciparum.
Parasite-derived proteins expressed on the surface of erythrocytes infected with Plasmodium falciparum are important virulence factors, since they mediate binding of infected cells to diverse receptors on vascular endothelium and are targets of a protective immune response. They are difficult to study because they undergo rapid clonal antigenic variation in vitro, which precludes the derivation of phenotypically homogeneous cultures. Here we have utilized sequence-specific proteases to dissect the role of defined antigenic variants in binding to particular receptors. By selection of protease-resistant subpopulations of parasites on defined receptors we (i) confirm the high rate of antigenic variation in vitro; (ii) demonstrate that a single infected erythrocyte can bind to intercellular adhesion molecule 1, CD36, and thrombospondin; (iii) show that binding to intercellular adhesion molecule 1 and CD36 are functions of the variant antigen; and (iv) suggest that binding to thrombospondin may be mediated by other components of the infected erythrocyte surface.
Gardner
J P
JP
Molecular Parasitology Group, Institue of Molecular Medicine, John Radcliffe Hospital, Oxford, England.
Pinches
R A
RA
Roberts
D J
DJ
Newbold
C I
CI
D000818:Animals; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000235:genetics*; D018955:CD36 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D010450:Endopeptidases / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000469:parasitology*; D004903:Erythrocyte Aggregation / Q000187:drug effects; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016778:Malaria, Falciparum / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D010641:Phenotype; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D019699:Thrombospondins; D014774:Virulence
D000953:Antigens, Protozoan; D018955:CD36 Antigens; D008562:Membrane Glycoproteins; D019699:Thrombospondins; D018799:Intercellular Adhesion Molecule-1; D010450:Endopeptidases