Identification of a major B-cell epitope of the Plasmodium falciparum glutamate-rich protein (GLURP), targeted by human antibodies mediating parasite killing.
The antigenicity of the glutamate-rich protein (GLURP) of Plasmodium falciparum was comprehensively evaluated in epitope-mapping studies utilizing a phage display library, synthetic peptides and anti-GLURP IgG preparations previously shown to promote strong antibody-dependent cellular inhibition (ADCI) effects. We identified six major B-cell epitopes within the nonrepetitive region R0, corresponding to amino acid residues 173 to 187 (P1), 193 to 207 (P3), 216 to 229 (P4), 264 to 288 (P11), 343 to 357 (P10), and 407 to 434 (S3). Of these, four (P1, P3, P4, and S3) were frequently recognized by high-titered IgG antibodies in plasma samples from immune Liberian adults (prevalence: 29.1-45.0%). The three epitopes P1, P3, and P4 contained a common motif (seven out of nine positions are identical) and may thus constitute a family of structurally related epitopes. This leaves two distinct epitopes, one (P3) representing this new epitope family and S3 as targets for biologically active antibodies. Human IgG antibodies from single plasma samples were affinity-purified against these peptides. P3-specific IgG preparations were consistently more effective in ADCI than S3-specific IgG. Among the different GLURP epitopes, we therefore suggest that the P3 epitope is potentially the most important epitope in GLURP for the development of clinical immunity to malaria in man.
Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark. mth@ssi.dk
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Theisen
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Soe
S G
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Jessing
L M
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Okkels
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Danielsen
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Oeuvray
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Druilhe
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Jepsen
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
D000913:Antibodies, Protozoan; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D010446:Peptide Fragments; D015800:Protozoan Proteins; C072492:glutamate-rich protein, Plasmodium