A Sequence in Subdomain 2 of DBL1? of Plasmodium falciparum Erythrocyte Membrane Protein 1 Induces Strain Transcending Antibodies

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 sequestrati...

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Autores:
Tipo de recurso:
Fecha de publicación:
2013
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/22840
Acceso en línea:
https://doi.org/10.1371/journal.pone.0052679
https://repository.urosario.edu.co/handle/10336/22840
Palabra clave:
Erythrocyte membrane protein 1
Protein antibody
Strain transcending antibody
Unclassified drug
Amino acid sequence
Antigen antibody reaction
Antigen binding
Article
Child
Disease severity
Erythrocyte
Female
Flow cytometry
Human
Immunofluorescence test
In vitro study
Malaria
Male
Nonhuman
Plasmodium falciparum
Preschool child
Protein binding
Protein domain
Protein motif
Amino acid motifs
Amino acid sequence
Animals
Antibody specificity
Cross reactions
Epitopes
Erythrocytes
Female
Humans
Immunoglobulin g
Infant
Male
Molecular sequence data
Peptides
Plasmodium falciparum
Protein binding
Protein conformation
Protein interaction domains and motifs
Protozoan proteins
Rabbits
Rats
Plasmodium falciparum
molecular
protozoan
protozoan
preschool
Antibodies
Antigens
Child
Models
Rights
License
Abierto (Texto Completo)
Description
Summary: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-DBL1? 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 DBL1?-domains were also found to react with the pRBC surface. By utilizing a peptide array to map the binding properties of the elicited anti-DBL1? 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. © 2013 Blomqvist et al.