Tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei.

The protozoan parasite Trypanosoma brucei evades clearance by the host immune system through antigenic variation of its dense variant surface glycoprotein (VSG) coat, periodically 'switching' expression of the VSG using a large genomic repertoire of VSG-encoding genes. Recent studies of antigenic variation in vivo have focused near exclusively on parasites in the bloodstream, but research has shown that many, if not most, parasites reside in the interstitial spaces of tissues. We sought to explore the dynamics of antigenic variation in extravascular parasite populations using VSG-seq, a high-throughput sequencing approach for profiling VSGs expressed in populations of T.