Antigenic variation in trypanosomes

We review here antigenic variation in African trypanosomes with emphasis on genetic mechanisms and on the expression sites in which the genes for Variant Surface Glycoproteins (VSGs) are expressed. There are multiple expression sites in a trypanosome, but only one of these is active at a time. We discuss recent experiments that provide new information on expression site regulation, i.e., how inactive sites are kept inactive and how the trypanosome switches from expression of one site to expression of another one. Trypanosomes can also change the gene expressed by replacing the gene in an active expression site by another VSG gene. This replacement involves the duplicative transposition of a silent VSG gene into the expression site. We present a model for the mechanism of this transposition that incorporates new features and that explains several unusual characteristics of the transposition process. We also discuss how new knowledge of nutrient uptake, notably uptake of host transferrin by trypanosomes, might be used for vaccine development.