Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes.
Plasmodium falciparum-infected human erythrocytes evade host immunity by expression of a cell-surface variant antigen and receptors for adherence to endothelial cells. These properties have been ascribed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), an antigenically diverse malarial protein of 200-350 kDa on the surface of parasitized erythrocytes (PEs). We describe the cloning of two related PfEMP1 genes from the Malayan Camp (MC) parasite strain. Antibodies generated against recombinant protein fragments of the genes were specific for MC strain PfEMP1 protein. These antibodies reacted only with the surface of MC strain PEs and blocked adherence of these cells to CD36 but without effect on adherence to thrombospondin. Multiple forms of the PfEMP1 gene are apparent in MC parasites. The molecular basis for antigenic variation in malaria and adherence of infected erythrocytes to host cells can now be pursued.
Baruch
D I
DI
Affymax Research Institute Santa Clara, California 95051, USA.
Pasloske
B L
BL
Singh
H B
HB
Bi
X
X
Ma
X C
XC
Feldman
M
M
Taraschi
T F
TF
Howard
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan; D000940:Antigenic Variation / Q000235:genetics; D015703:Antigens, CD / Q000378:metabolism; D000953:Antigens, Protozoan / Q000235:genetics*; D001798:Blood Proteins / Q000235:genetics* / Q000276:immunology; D018955:CD36 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D016054:DNA, Protozoan / Q000032:analysis; D004910:Erythrocyte Membrane / Q000469:parasitology*; D017125:Genes, Protozoan / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins / Q000276:immunology; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D019699:Thrombospondins
D000913:Antibodies, Protozoan; D015703:Antigens, CD; D000953:Antigens, Protozoan; D001798:Blood Proteins; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D016054:DNA, Protozoan; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D019699:Thrombospondins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum