Discussion

Antigenic variation of the Variant Surface Glycoprotein (VSG) is the mechanism by which African trypanosomes (Trypanosoma brucei, T. congolense and T. vivax) survive the humoral immune response of their vertebrate host during the bloodstream stage. The VSG is encoded by a multi-copy gene family, with many hundreds of variants available to the parasite. Understanding the origins of this antigenic diversity, which is so crucial to parasite survival, and analysing it from genome or transcriptome sequence data are major challenges that we are addressing. I will present data describing the scale of variation in VSG genomic repertoire across natural populations of T. congolense and T. vivax. By defining the limits of antigenic diversity in T. congolense and T. vivax, it is possible to compare VSG repertoires on a population scale using conserved VSG phylotypes in an approach we call ‘Variant Antigen Profiling’. Quantifying population variation also provides an opportunity to examine the molecular evolution of antigenic diversity, and test the hypothesis that differences in recombination rate between species result in different levels of sequence variation. By multiple tests of sequence contiguity, I will show how sequence mosaicism is predicted to be extremely frequent among T. brucei VSG, less so among T. congolense (though still considerable) and rare among T. vivax VSG. Progress is being made towards delimiting what might be called the ‘VSG universe’, with respect to structural diversity, analytical methods and the mechanisms responsible for generating novel antigens.