Properties of epitopes of Pfs 48/45, a target of transmission blocking monoclonal antibodies, on gametes of different isolates of Plasmodium falciparum.
We have studied the properties of epitopes on Plasmodium falciparum gamete surface protein Pfs 48/45, a target antigen of malaria transmission blocking antibodies. Using a two site immunoradiometric assay we have defined three spacially separate, non-repeated, epitope regions on the peptides representing this antigen. Epitope region I is a target of monoclonal antibodies (MoAbs) which strongly suppress infectivity of gametocytes of P. falciparum to mosquitoes; the effect is complement independent and is mediated as effectively by the monovalent Fab fragments as by intact MoAb. Epitope region II consists of two spacially close subregions, IIa and IIb; variant forms of epitopes IIa and IIb occurred in different isolates of P. falciparum. Epitope region III also showed slight structural modification between isolates. MoAbs against regions II or III were relatively ineffective in suppressing gametocyte infectivity compared to MoAbs against region I. However, certain combinations of MoAbs against regions II and III together acted synergistically to suppress infectivity to mosquitoes. All these epitopes failed to react with MoAb when the antigen was presented in reduced form. A fourth epitope, however, was identified which reacted strongly with MoAb when the antigen was presented in reduced form. The MoAb against this epitope had no effect on the infectivity of gametocytes of P. falciparum to mosquitoes.
Carter
R
R
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Graves
P M
PM
Keister
D B
DB
Quakyi
I A
IA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000953:Antigens, Protozoan / Q000032:analysis / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000032:analysis / Q000276:immunology*; D008288:Malaria / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D008565:Membrane Proteins / Q000276:immunology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D011233:Precipitin Tests; D011863:Radioimmunoassay
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000939:Epitopes; D008565:Membrane Proteins