Characterization of two vaccinia CD36 recombinant-virus-generated monoclonal antibodies (10/5, 13/10): effects on malarial cytoadherence and platelet functions.
Extensive evidence is now available to show that the human CD36 antigen is a cellular receptor for thrombospondin, collagen, modified low-density lipoproteins, and long-chain fatty acids. Moreover, CD36 functions as one of the receptors that mediates the adhesion of Plasmodium-falciparum-infected erythrocytes to microvascular endothelium. In an attempt to identify new functional sites of this surface glycoprotein, anti-CD36 monoclonal antibodies were prepared using a vaccinia CD36 recombinant virus as a highly efficient immunization vector. In functional studies, one of these antibodies (clone 10/5) strongly inhibited the adhesion of P. falciparum-infected erythrocytes to purified CD36. This antibody also potentiated ADP-induced platelet activation. In contrast, a second antibody (clone 13/10) did not affect the cytoadherence of infected erythrocytes or platelet functions. Previous structural work performed on these antibodies has shown that clone 10/5 is directed against an epitope within the CD36 domain 155-183, whereas clone 13/10 interacts with another antigenic determinant defined by amino acids 30-76 [Daviet, L., Buckland, R., Puente Navazo, M. D. & McGregor, J. L. (1995) Biochem. J. 305, 221-224]. Taken together, these current studies show that: (a) the methodology of immunization using recombinant vaccinia virus is a powerful tool in the generation of monoclonal antibodies directed against polyimmunogenic membrane glycoproteins such as CD36; (b) the CD36 domain, recognized by clone 10/5 but not by 13/10, is functionnally important regarding the adhesion of P. falciparum-infected erythrocyte and CD36-dependent platelet activation.
Daviet
L
L
INSERM Unit 331, Faculty of Medicine RTH Laënnec, Lyon, France.
Craig
A G
AG
McGregor
L
L
Pinches
R
R
Wild
T F
TF
Berendt
A R
AR
Newbold
C I
CI
McGregor
J L
JL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001792:Blood Platelets / Q000502:physiology*; D018955:CD36 Antigens / Q000276:immunology* / Q000502:physiology; D002448:Cell Adhesion; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D007114:Immunization / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D015539:Platelet Activation; D011994:Recombinant Proteins / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D011994:Recombinant Proteins