Cytoadherence-related neoantigens on Plasmodium falciparum (human malaria)-infected human erythrocytes result from the exposure of normally cryptic regions of the band 3 protein.
Murine 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.
University of California, Riverside 92521.
I
I
Crandall
I W
IW
Sherman
D000595:Amino Acid Sequence; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000737:chemistry / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000276:immunology; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D006825:Hybridomas; D018328:Melanoma, Amelanotic; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology*; D014357:Trypsin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001457:Anion Exchange Protein 1, Erythrocyte; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D014357:Trypsin