Identification of a 67‐amino‐acid region of the Plasmodium falciparum variant surface antigen that binds chondroitin sulphate A and elicits antibodies reactive with the surface of placental isolates

• Published in: Molecular microbiology Vol. 53; no. 2; pp. 445 - 455
• Main Authors: Gamain, Benoit, Smith, Joseph D., Avril, Marion, Baruch, Dror I., Scherf, Artur, Gysin, Jurg, Miller, Louis H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.2004; Blackwell Science; Blackwell Publishing Ltd
• Subjects: Amino Acid Sequence; Animals; Antibodies, Protozoan - blood; Antibodies, Protozoan - immunology; Antigens, Protozoan - chemistry; Antigens, Protozoan - genetics; Antigens, Protozoan - immunology; Antigens, Protozoan - metabolism; Biological and medical sciences; CD36 Antigens - metabolism; Cell Adhesion; Cell Line; Chondroitin Sulfates - metabolism; Conserved Sequence; Cricetinae; Fundamental and applied biological sciences. Psychology; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - immunology; Membrane Proteins - metabolism; Microbiology; Phylogeny; Plasmodium falciparum; Plasmodium falciparum - immunology; Plasmodium falciparum - pathogenicity; Protein Binding; Protein Structure, Tertiary; Protozoan Proteins - chemistry; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Protozoan Proteins - metabolism; Rabbits; Sequence Homology; Structure-Activity Relationship; Antigen; Protozoa; Plasmodium falciparum; Apicomplexa; Microbiology; Antibody; Isolate; Identification
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/j.1365-2958.2004.04145.x

Summary The complications of malaria in pregnancy are caused by the massive sequestration of parasitized erythrocytes (PE) in the placenta. Placental isolates of Plasmodium falciparum are unusual in that they do not bind the primary microvasculature receptor CD36 but instead bind chondroitin sulphate A (CSA). Pregnant mothers develop antibodies that recognize placental variants worldwide, suggesting that a vaccine against malaria in pregnancy is possible. Some members of the Duffy binding‐like γ (DBL‐γ) domain of the large and diverse P. falciparum erythrocyte membrane protein‐1 (PfEMP‐1) family, when expressed on Chinese hamster ovary (CHO) cells, bind CSA. To characterize better the molecular requirements for DBL‐γ adhesion to CSA, we determined the binding of various DBL‐γ domains. Most DBL‐γ did not bind CSA, and no conserved region was identified that strictly differentiated binders from non‐binders. Structure–function analysis of the FCR3‐CSA DBL‐γ domain localized the minimal CSA binding region to a 67‐residue fragment. This region was partially conserved among some binding sequences. Serum from a rabbit immunized with the minimal domain reacted with CSA‐binding parasite lines, but not with non‐CSA‐adherent PE lines that adhered to CD36 and other receptors. The identification of a minimal binding region from a highly variable cytoadherent family may have application for a vaccine against malaria in pregnancy.