Unknown

Dataset Information

0

African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.


ABSTRACT: The African trypanosome Trypanosoma brucei spp. is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity. The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs. This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture. We establish here that this model does not account for the scope of VSG structural and biochemical diversity. The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state. The structure also reveals an O-linked carbohydrate on the top surface of VSG3. Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs. We demonstrate that this O-glycosylation increases parasite virulence by impairing the generation of protective immunity. These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.

SUBMITTER: Pinger J 

PROVIDER: S-EPMC6108419 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications


The African trypanosome Trypanosoma brucei spp. is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity. The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs. This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VS  ...[more]

Similar Datasets

| S-EPMC4697842 | biostudies-literature
| S-EPMC4922192 | biostudies-literature
| S-EPMC1864976 | biostudies-literature
| S-EPMC2941730 | biostudies-literature
| S-EPMC9279368 | biostudies-literature
| S-EPMC8748868 | biostudies-literature
| S-EPMC3605285 | biostudies-literature
| S-EPMC2805297 | biostudies-literature
| S-EPMC9472816 | biostudies-literature
| S-EPMC5635023 | biostudies-literature