title: A sequence in subdomain 2 of DBL1α of Plasmodium falciparum erythrocyte membrane protein 1 induces strain transcending antibodies.
abstract: Immunity to severe malaria is the first level of immunity acquired to Plasmodium falciparum. Antibodies to the variant antigen PfEMP1 (P. falciparum erythrocyte membrane protein 1) present at the surface of the parasitized red blood cell (pRBC) confer protection by blocking microvascular sequestration. Here we have generated antibodies to peptide sequences of subdomain 2 of PfEMP1-DBL1α previously identified to be associated with severe or mild malaria. A set of sera generated to the amino acid sequence KLQTLTLHQVREYWWALNRKEVWKA, containing the motif ALNRKE, stained the live pRBC. 50% of parasites tested (7/14) were positive both in flow cytometry and immunofluorescence assays with live pRBCs including both laboratory strains and in vitro adapted clinical isolates. Antibodies that reacted selectively with the sequence REYWWALNRKEVWKA in a 15-mer peptide array of DBL1α-domains were also found to react with the pRBC surface. By utilizing a peptide array to map the binding properties of the elicited anti-DBL1α antibodies, the amino acids WxxNRx were found essential for antibody binding. Complementary experiments using 135 degenerate RDSM peptide sequences obtained from 93 Ugandan patient-isolates showed that antibody binding occurred when the amino acids WxLNRKE/D were present in the peptide. The data suggests that the ALNRKE sequence motif, associated with severe malaria, induces strain-transcending antibodies that react with the pRBC surface.
authors: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors: Karin
authors: K
authors: Blomqvist
authors: Letusa
authors: L
authors: Albrecht
authors: Maria del Pilar
authors: Mdel P
authors: Quintana
authors: Davide
authors: D
authors: Angeletti
authors: Nicolas
authors: N
authors: Joannin
authors: Arnaud
authors: A
authors: Chêne
authors: Kirsten
authors: K
authors: Moll
authors: Mats
authors: M
authors: Wahlgren
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D002675:Child, Preschool; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007223:Infant; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits; D051381:Rats
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D007074:Immunoglobulin G; D010455:Peptides; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum