Withstanding the Challenges of Host Immunity: Antigenic Variation and the Trypanosome Surface Coat
Prolonged survival in the face of host immunity has been a major force shaping the biology and evolution of the African trypanosomes, and nowhere are the effects of this force more apparent than in the antigenic variation of the trypanosome variant surface glycoprotein (VSG) coat. The coat protects the trypanosome within it from immune effectors, and spontaneous and stochastic events occurring at the molecular level cause individual trypanosomes to change the VSG variant they are expressing. The consequence of this switching at the population level is a diverse population that can pre-empt the specific immune responses that arise against VSG. The template for changes to VSG is an extensive archive of silent VSG genes and pseudogenes. VSG from the archive are activated not only as full-length genes but also through the combination of segments to form mosaic VSG genes, a process that augments the potential for antigenic variation by introducing combinatorial variation and allowing VSG pseudogenes to be used. The main part of the archive occupies subtelomeres and so is itself prone to mutation and rapid evolution, which are important features when superinfection or reinfection of partially immune hosts is necessary. The antigenic variation ‘diversity phenotype’ is thus a multifaceted one, enlisting and coordinating fundamental mechanisms of cell biology to bring about a process that unfolds across populations, thereby facilitating the success of the African trypanosomes.
KeywordsAntigenic Variation Expression Site Monoallelic Expression Variant Surface Glycoprotein Trypanosome Infection
This chapter is based on theses deposited at the University of Glasgow (J. P. J. Hall 2012; L. Plenderleith 2013). We would like to thank Dave Barry for his support, guidance and advice throughout our studies. This work was supported by the Wellcome Trust (Grant numbers 083224 and 086415). The Wellcome Trust Centre for Molecular Parasitology is supported by core funding from the Wellcome Trust (Grant number 085349).
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