Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies.
The CD36 molecule expressed by human endothelial cells is a receptor for the adhesion of erythrocytes infected with the human malaria parasite Plasmodium falciparum. A CD36-specific monoclonal antibody, OKM8, inhibits the adhesion of malaria-infected erythrocytes (IRBC) to purified CD36 and cells expressing CD36. Monospecific polyclonal anti-idiotype (anti-Id) antibodies, raised against monoclonal antibody OKM8, expressed determinants molecularly mimicking the CD36 binding domain for the adhesion of IRBC. Purified rabbit anti-Id antibodies reacted with the surface of IRBC by immunofluorescence, directly supported the adhesion of wild-type P. falciparum malaria isolates, and inhibited IRBC cytoadherence to melanoma cells. An approximately 270-kDa protein was immunoprecipitated by the anti-Id antibodies from surface-labeled and metabolically labeled IRBC and was competitively inhibited by soluble CD36. These results support the hypothesis that CD36 is a receptor and the approximately 270-kDa protein, sequestrin, is a complementary ligand involved in the adhesion of IRBC to host-cell endothelium. Sequestrin is a candidate malaria vaccine antigen, and anti-Id antibodies that recognize this molecule may be useful for passive immunotherapy of cerebral and severe P. falciparum malaria.
Ockenhouse
C F
CF
Department of Medicine, Walter Reed Army Medical Center, Washington, DC.
Klotz
F W
FW
Tandon
N N
NN
Jamieson
G A
GA
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism*; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology*; D007130:Immunoglobulin Idiotypes; D008545:Melanoma / Q000378:metabolism; D010963:Plasmodium falciparum / Q000276:immunology / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011233:Precipitin Tests; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000953:Antigens, Protozoan; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D007130:Immunoglobulin Idiotypes; D010980:Platelet Membrane Glycoproteins