Antigenic Diversity and Immune Evasion by Malaria Parasites

Evolution of allelic dimorphism in malarial surface antigens

“…As the dimorphic domains of MSP-1 (blocks 6-16) contain significant stretches of conserved sequence (Figure 1), which would afford ample opportunity for occasional recombination, the absence of recombinants (Tanabe et al, 1987;Miller et al, 1993) seems very likely to be due to selective disadvantage. Suppression of recombination between alleles encoding highly divergent antigenic variants is the expected outcome if variant-specific immunity plays a major role in parasite clearance (Ferreira et al, 2004); parasites expressing hybrid variants of surface proteins, with antigenic determinants derived from both major dimorphic types, would be recognized by hosts previously exposed to either dimorphic type, reducing their fitness (McKenzie et al, 2001). Recombination creates a clear distinction between nonrecombining dimorphic domains (which are quite likely to closely correspond to immunodominant domains under balancing selection) and the conserved flanking regions, which have been homogenized by recombination events (Figure 1).…”

“…The extensive polymorphism of surface antigens is one of the major factors why immunity to malaria, in contrast to most viral and bacterial infections, develops only after repeated infections with the same species (Ferreira et al, 2004). Not surprisingly, genes encoding these antigens are under strong diversifying selection (Hughes, 1992;Hughes and Hughes, 1995;Escalante et al, 1998), whereas synonymous nucleotide sites and non-coding nuclear DNA sequences, which are thought to be selectively neutral, are mostly conserved (Hartl, 2004).…”

“…There are two distinct forms of antigenic diversity in malaria parasites: (a) the classical genetic mechanisms of mutation and recombination create allelic polymorphism, the existence of multiple genetically stable alternative forms of antigen-coding genes; (b) the sequential expression of alternate forms of an antigen by the same clonal parasite lineage leading to antigenic variation, which characterizes some antigens (such as PfEMP-1 and rifins) exported by the parasite to the surface of infected red blood cells (Ferreira et al, 2004). Blood-stage surface antigens of P. falciparum may show a specific pattern of allelic polymorphism in which all observed alleles are clearly divided into two allelic classes, such that alleles within a class are much less divergent than are alleles from different classes.…”

Stable allele frequency distribution of the polymorphic region of SURFIN4.2 in Plasmodium falciparum isolates from Thailand

“…The erythrocytic cycle of Plasmodium falciparum is characterized by complex interactions between parasite-derived surface exposed antigens, host-cell receptors and immune defense proteins. Parasite adhesins expressed on the surface of malaria-infected erythrocytes provide adhesive properties and at the same time allow for host immune evasion by virtue of antigenic variation and antigenic polymorphism [2]. Recently, a new multigene family called surf was identified, consisting of at least 10 members in the genome of P. falciparum 3D7 parasite line and infected erythrocyte surface localization was shown for one of the member, SURFIN 4.2 (gene ID: PFD1160w, chr 4) [3].…”

Synchronous versus asynchronous oscillations for antigenically varyingPlasmodium falciparumwith host immune response

“…The parasite's ability to alter exposed antigens is called antigenic variation; this prevents the IR from maintaining a prolonged attack against any single variant [5,11,25]. For Pf the variation occurs in the antigen PfEMP1 and, more specifically, variations in its unique IR-binding site referred to as its major epitope [27].…”