Antigenic Variation Flashcards
(29 cards)
What are contingency genes?
A special class of genes that enable rapid changes in a microbe’s phenotype, allowing it to adapt to changing environments or host immune responses
What is the mutation rate of contingency genes?
Hypermutation (10^-2 - 10^-3)
What does it mean for contingency gene mutations to be “pre-emptive”?
They are no in reaction/triggered by immune pressures. They occur before hand, and allow pathogens to be ready for the changing host environment
What are the 3 principles of antigenic variation?
- Only one variable surface antigen is expressed at one time by one cell
- The pathogen is capable of switching expression to another antigen
- The pathogen contains a family of variable antigen genes to allow switching
What are some mechanisms that allow hypermutation of contingency genes?
- Promoter inversion
- Gene conversion
- Gene transposition
What are variant surface glycoproteins?
VSGs make up the dense uniform coat of T. brucei
What is the role of VSG coat in T brucei?
- Has no known enzymatic or structural role, beyond purely acting as an immune shield
- Sterically blocks antibodies from accessing invariant surface proteins underneath (e.g. nutrient transporters)
What are the two mechanisms of VSG switching in T. brucei?
- Transcriptional switching
- Gene conversion
What are BES?
Bloodstream Expression Sites, found on telomeres
How many BESs does T. brucei have?
Around 15
What does each bloodstream expression site have?
Each BES has its own promotor, and contains a VSG gene
Where does active transcription of BES occur?
In the expression site body
What is transcription of VSG gene driven by?
RNA polymerase I
How does transcriptional switching occur?
One BES is removed from the expression site body, turning it off, and another is recruited and transcribed
How does transcriptional switching mechanism ensure mono-allelic expression?
Only one VSG expression site can be recruited and present in the expression site body at one time.
All other VSG expression sites are transcriptionally silenced
What is the significance of transcriptional switching?
- Provides quick switch using pre-assembled BESs
- Limited by the number of BESs (15), so not enough to sustain long term infection on their own
What is the VSG archive?
Made up of thousands of silent genes and pseudogenes
Where are genes in the VSG archive found?
- Chromosome-internal arrays
- Mini chromosomes
- Subtelomeric regions
How does gene conversion work wrt VSG antigenic variation?
Instead of switching pre made BESs, the parasite copies a new silent VSG gene from its vast archive into the active site
What is the mechanism involved in gene conversion?
Homologous recombination
What is important in mediated gene switching?
Rad51.
Gene conversion is Rad51-dependent homologous recombination
Why is gene switching significant?
- Allows access to full VSG archive
- Allows formation of mosaic VSGs from psuedogenes
- Enables virtually limitless variation, allowing the parasite to sustain infection
What does using both allow T. brucei to balance?
VSG…
- Speed (BES switching)
- Diversity and longevity (gene conversion)
What is the reality of VSG switching in a population of T. brucei?
It will be a heterogenous population, with different parasite cells expressing different VSG
