A fourth family of the Plasmodium falciparum S-antigen

The S-antigen of Plasmodium falciparum is a highly diverse heat stable protein that is located in the parasitophorous vacuole of the mature asexual intraerythrocytic parasite. The gene for S-antigen exists within the parasite population as multiple alleles at a single locus. Its sequence contains a large central block of tandemly arranged peptides that are identical or very similar in one allele but differ widely in sequence, repeat length and number among different alleles, and consequently antigenic specificity. Thus, antibodies directed against the repeat region can be used to define the serotype of an S-antigen. Flanking this repeat block are 2 short regions of non-repetitive sequence which have been described as occurring in three different forms, each of which is used to define a single S-antigen family. We present the S-antigen sequence for the isolate 3D7 which defines not only a novel serotype but also a novel S-antigen family. The central repeat block is composed of 57 copies of an 8-residue peptide with consensus sequence ED(E/K)VSNG(R/G). Comparison of the four S-antigen families reveals that they differ considerably from each other with variation being most pronounced in the carboxy terminal-flanking region. This pattern of sequence variation differs considerably from that found for MSA-1 and MSA-2, the only other diverse proteins of P. falciparum for which sequence information is available.