Variant surface glycoprotein

Variant surface glycoprotein (VSG) is a ~60kDa protein which densely packs the cell surface of protozoan parasites belonging to the genus Trypanosoma. This genus is notable for their cell surface proteins. They were first isolated from Trypanosoma brucei in 1975 by George Cross. VSG allows the trypanosomatid parasites to evade the mammalian host's immune system by extensive antigenic variation. They form a 12–15 nm surface coat. VSG dimers make up ~90% of all cell surface protein and ~10% of total cell protein. For this reason, these proteins are highly immunogenic and an immune response raised against a specific VSG coat will rapidly kill trypanosomes expressing this variant. However, with each cell division there is a possibility that the progeny will switch expression to change the VSG that is being expressed. VSG has no prescribed biochemical activity. The parasite has a large cellular repertoire of antigenically distinct VSGs (~1500/2000 complete and partial (pseudogenes)) located in telomeric and subtelomeric arrays (on megabase chromosomes or minichromosomes). VSGs are expressed from a bloodstream expression site (BES, ES) in a polycistron by RNA polymerase I (recruited to a ribosomal-type promoter) with other ES-associated genes (ESAGs), of which transferrin receptor (Tfr: ESAG6, ESAG7) is one. Only one VSG gene is expressed at a time, as only one of the ~15 ES are active in a cell. VSG expression is 'switched' by homologous recombination of a silent basic copy gene from an array (directed by homology) into the active telomerically-located expression site. During this transition, trypanosomes simultaneously display both pre- and post-switch VSGs on their surface. This coat replacement process is critical for the survival of recently switched cells because initial VSGs remain targets for the escalating host Ab response. Mosaic VSG genes can be created by homologous recombination of a partial VSG gene from an array. This partial gene may replace any portion of the residing VSG gene, creating a new mosaic VSG.