Plasmodium falciparum-infected erythrocyte adhesion to the type 3 repeat domain of thrombospondin-1 is mediated by a modified band 3 protein

A monoclonal antibody, 1C4, was produced which recognizes a 65 kDa protein that is localized to the plasma membrane of human erythrocytes infected with Plasmodium falciparum. By immunofluorescence the antigen was visualized as dots on the surface of the infected cell. The 65 kDa protein was present in 4 strains of diverse geographical origin, and in erythrocytes infected with a knobless strain. The 65 kDa protein was insoluble in non-ionic detergents, but was partly soluble in SDS and some high (1 M) śalt solutions. The 65 kDa protein is recognized by antibodies specific for the cytoplasmic domain and the N-terminal side of the membrane-spanning region of human band 3, but was not recognized by an antibody specific to the C-terminal side of the membrane-spanning region. The results of treatment of the 65 kDa protein with trypsin and chymotrypsin are consistent with the 65 kDa protein being a truncated and covalently modified band 3 molecule which consists of the first 540 amino acids of human band 3.

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Cytoadherence-related homologous motifs inPlasmodium falciparumantigen Pf155/RESA and erythrocyte band 3 protein

Parasitology ◽

10.1017/s0031182000065215 ◽

1995 ◽

Vol 110 (5) ◽

pp. 503-511 ◽

Cited By ~ 9

Author(s):

J. Iqbal ◽

A. B. Siddique ◽

N. Ahlborg ◽

P. Perlmann ◽

K. Berzins

Keyword(s):

Plasmodium Falciparum ◽

Cell Surface ◽

Synthetic Peptides ◽

Molecular Basis ◽

Band 3 ◽

Cell Surface Molecules ◽

Band 3 Protein ◽

Surface Molecules ◽

Erythrocyte Antigen

SUMMARYCytoadherence ofPlasmodium falciparum-infected erythrocytes plays an important role in the pathogenesis of cerebral malaria. The identity of cell surface molecules on parasitized erythrocytes involved in cytoadherence is of great interest to understand the molecular basis of this mechanism. Peptide sequences derived from exofacial loops of the erythrocyte antigen band 3 from parasitized erythrocytes have previously been shown to inhibit cytoadherence. We now report that a non-repeated region of Pf155/RESA (residues 213–218) contains a hexapeptide motif being highly homologous to cytoadherence inhibitory sequences from band 3. Synthetic peptides containing the hexapeptide motif of Pf155/RESA inhibited the binding ofP.falciparum-infected erythrocytes to melanoma cellsin vitro. Furthermore, individuals residing in malaria-endemic areas have antibodies reactive with epitopes involving these motifs in band 3 and in Pf155/RESA.

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Cytoadherence-related neoantigens on Plasmodium falciparum (human malaria)-infected human erythrocytes result from the exposure of normally cryptic regions of the band 3 protein

Parasitology ◽

10.1017/s0031182000076101 ◽

1994 ◽

Vol 108 (3) ◽

pp. 257-267 ◽

Cited By ~ 32

Author(s):

I. Crandall ◽

I. W. Sherman

Keyword(s):

Plasmodium Falciparum ◽

Protein Band ◽

Band 3 ◽

Amelanotic Melanoma ◽

Red Cells ◽

Sequence Motif ◽

Red Cell ◽

Band 3 Protein ◽

Red Cell Membranes

SUMMARYMurine monoclonal antibodies (Mabs) were produced by vaccination of Balb/c mice with live Plasmodium falciparum infected red cells (iRBC). The iRBC Mabs recognized altered forms of the human erythrocyte membrane protein band 3; however, these Mabs did not recognize the band 3 molecule in uninfected or ring-infected red cells. The location of epitopes was determined by studying the binding of the iRBC Mabs after selective proteolysis of band 3 as well as by the reactivity of these Mabs to synthetic peptides that corresponded to putative exofacial regions of band 3. Treatment of uninfected red cell membranes with trypsin under low ionic strength conditions resulted in exposure of cryptic epitopes of band 3 which were recognized by the iRBC Mabs. Several of the anti-iRBC Mabs (two of which were described previously) inhibited the in vitro adherence of infected erythrocytes to C32 amelanotic melanoma cells. A mouse polyclonal serum against a synthetic peptide based on an amino acid sequence motif of band 3 reacted (by immunostaining) only with the surface of iRBC and blocked adhesion. Thus, it appears that cryptic residues of the band 3 protein become exposed upon parasitization, and their presence contributes to the increased adhesiveness of the P. falciparum-infected red cell.

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