Antigenic Variation in Malaria

Abstract

Antigenic variation of malaria parasites was discovered in P. knowlesi, using a schizont-infected cell agglutination (SICA) assay to detect variant antigens expressed at the surface of infected erythrocytes. Later studies utilizing stable clones, Pk1(A+) and its direct derivative, Pk1(B+)1+, showed that SICA[+] clones express distinct parasite-encoded antigens of approximately 200 kDa. Here we identify a P. knowlesi variant antigen gene and cDNA and demonstrate that it encodes the 205 kDa variant antigen expressed by B+ parasites. This gene belongs to a multigene family, which we term SICAvar. Its ten-exon structure with seven cysteine-rich coding modules is unique compared to P. falciparum var genes. Further, we highlight a 3' genomic alteration that we predict is related to SICAvar gene switching.

Contribution of Plasmodium knowlesi to Multispecies Human Malaria Infections in North Sumatera, Indonesia

“…SICAvar genes encode an antigen family unique to P. knowlesi , estimated to number >100 members, including both multiexon and truncated forms randomly distributed across all 14 chromosomes [23]. SICAvar proteins undergo antigenic variation in the course of a single infection [26, 27] and are likely to play a key role in maintaining chronic parasitemia in semi-immune hosts. Sequencing of a handful of sicavar amplicons from our samples confirmed nucleotide diversity in our short target sequence, double peaking indicative of multiple loci being amplified in some cases, and distinguished a variant form with a 7–amino acid insert (Figure 3).…”

Jumbled Genomes: Missing Apicomplexan Synteny

“…Gene creation has been vital in the development of virulence in the Apicomplexa. Species-specific antigen variation genes are present in multiple copies, especially in Plasmodium and Piroplasm species (al-Khedery et al 1999; Carlton et al 2002; Gardner et al 2002, 2005; Pain et al 2005). …”

Malaria Parasites: The Great Escape

“…Antigens prone to antigenic variation are often expressed on the surface of iRBC. Examples includes the multigene family, such the var genes (62), the stevor gene family, the rifin gene family (63), the surfin gene family (132), the sicavar gene family (133), and the Plasmodium interspersed repeats ( pir ) genes. The var gene family is the most studied and has been shown to be the target of protective anti-blood-stage antibodies (134, 135).…”