Characterization of domains of the phosphoriboprotein P0 of Plasmodium falciparum.
Antibodies against the amino-terminal domain of the Plasmodium falciparum P0 phosphoriboprotein were detected extensively in immune people living in malaria endemic areas of India. It has been shown earlier that specific antibodies raised against the PfP0N domain (17-61 amino acid) of the PfP0 protein inhibit P. falciparum growth in vitro. To study the properties of the rest of the protein, the remaining 61-316 amino acids on the carboxy-side of the PfP0 protein were expressed as a glutathione-S-transferase fusion protein (PfP0C). Antibodies raised against PfP0C identified the 38 kDa P0 protein on a parasite Western blot analysis. An ELISA assay using both the PfP0N and PfP0C fusion proteins showed no reactivity with malaria patient sera samples, but showed extensive reactions with the immune sera. Antibodies against both the PfP0C and PfP0N domains were raised in rabbits and different inbred strains of mice. T-cells from immunized mice showed lymphoproliferation when presented with PfP0 protein domains. IgG from both anti-PfP0N and anti-PfP0C sera inhibited the growth of P. falciparum in vitro in a concentration dependent manner. The IgG did not show any significant effect on the growth of intraerythrocytic stages, but specifically inhibited re-invasion of red cells. Merozoites and sexual stages showed surface reactivity to both anti-PfP0N and anti-PfP0C antibodies in immunofluorescence assays. These properties strongly indicate PfP0 as a possible target for invasion-blocking antibodies.
Chatterjee
S
S
Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai, India.
Singh
S
S
Sohoni
R
R
Kattige
V
V
Deshpande
C
C
Chiplunkar
S
S
Kumar
N
N
Sharma
S
S
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; C054675:ribosomal protein P0; D005982:Glutathione Transferase