Band 3 clustering promotes the exposure of neoantigens in Plasmodium falciparum-infected erythrocytes.

Erythrocytes infected with the human malaria parasite Plasmodium falciparum become structurally and antigenically modified as a consequence of intracellular parasite development. The new antigens that appear on the surface of the infected erythrocyte originate from parasite-encoded proteins and by modification of the erythrocyte membrane protein band 3. Here, we show that anti-peptide antibodies generated against an amino acid sequence (YETFSKLIKIFQDH) of human band 3, and previously identified as mediating adhesion of infected erythrocytes to CD36, recognized P.

Malaria infection induces a conformational change in erythrocyte band 3 protein.

Sequestration in the microvessels of the deep tissues is a signal characteristic of the human malaria Plasmodium falciparum. The adhesion of P. falciparum-infected cells to the post-capillary endothelial cells in various tissues contributes to both the pathology of the disease (i.

Chemical modifications of band 3 protein affect the adhesion of Plasmodium falciparum-infected erythrocytes to CD36.

The role of the erythrocyte anion exchanger, band 3 protein (AE1), in the adhesion of Plasmodium falciparum-infected erythrocytes to CD36 and thrombospondin (TSP) was studied. Two specific anion exchange inhibitors that bind covalently to different regions of the band 3 molecule affected cytoadherence in dissimilar ways. Modification of lysine 539 by diisothiocyanostilbene sulfonic acid (DIDS) resulted in a significant reduction in the adhesive properties of parasitized erythrocytes for CD36, but not TSP, whereas treatment with fluorescein-5-maleimide, which modifies lysine 430, was without effect on both TSP and CD36 binding.

Plasmodium falciparum-infected erythrocytes bind to the RGD motif of fibronectin via the band 3-related adhesin.

Previously it was shown that Plasmodium falciparum-infected erythrocytes bound to thrombospondin by the interaction of the peptidic sequence, HPLQKTY, of the band 3 protein of infected erythrocytes, and the RGD motif of thrombospondin. Here, we show that falciparum-parasitized erythrocytes bind to immobilized fibronectin by the RGD sequence of fibronectin. Involvement of the HPLQKTY region of band 3 in binding was demonstrated by inhibition of adhesion of parasitized erythrocytes to fibronectin by an HPLQKTY-containing peptide and the binding of the HPLQKTY peptide to the RGD sequence of immobilized fibronectin.

Identification of peptides targeting the surface of Plasmodium falciparum-infected erythrocytes using a phage display peptide library.

Drastic changes in the plasma membrane of Plasmodium falciparum-infected red blood cells (iRBCs) make the surface of iRBCs distinct from that of the uninfected erythrocyte. To identify small peptides that would specifically recognize the altered surface of iRBCs, we screened a phage display peptide library (PDL) on the surface of iRBCs. After the sixth panning of the PDL, eight phage clones of 18 sequenced clones had the same sequence, LVDAAAL (named P1) and specific binding of P1 to the surface of iRBCs was confirmed using phage expressing P1 peptides and synthetic P1 peptide.

Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind.

Infected erythrocytes containing the more mature stages of the human malaria Plasmodium falciparum may adhere to endothelial cells and uninfected red cells. These phenomena, called sequestration and rosetting, respectively, are involved in both host pathogenesis and parasite survival. This review provides a critical summary of recent advances in the characterization of the molecules of the infected red blood cell involved in adhesion, i.

Cytoadherence of malaria-infected red blood cells involves exposure of phosphatidylserine.

Phosphatidylserine (PS) is a membrane phospholipid which in intact cells is exclusively localized in the inner leaflet of the lipid bilayer. However, once cells undergo apoptosis or oxidative stress, PS molecules are exposed on the external surface of the cells and this contributes to their adherence to macrophages or endothelial cells. PS exposure on Plasmodium falciparum-infected red cells was determined by flow cytometry using fluorescein-labeled annexin V, which specifically binds to PS.