Biased amino acid composition in repeat regions of Plasmodium antigens

Many malarial antigens contain extensive arrays of tandemly repeated short amino acid sequences, and much of the antibody response induced by malaria infections is directed against these repeats. Indeed, it has been hypothesized that these repeats function to elicit a relatively ineffective T-cell-independent antibody response by the host. In order to test this hypothesis, tandem repeats of Plasmodium species were examined for a bias in composition favoring amino acids likely to form epitopes for the antibody. The genome of Plasmodium is very A+T-rich, and nucleotide compositional bias will, in itself, lead to a high proportion of hydrophilic amino acids. When this bias was controlled for, Plasmodium antigens did not show a higher proportion of hydrophilic amino acids than expected, but there was a significant reduction in the proportion of hydrophobic amino acids in the repeats of the antigens. The amino acid composition of the repeats was thus strikingly different from those seen both in the remainder of the antigens and in a sample of Plasmodium falciparum housekeeping genes.