Antigenic Variation

Question 1

What is antigenic variation?

Answer 1

The process of altering surface antigens in order to escape host adaptive immunity

Question 2

What are the 3 principles of antigenic variation?

Answer 2

• Only one variable surface antigen expression by the pathogen in one cell at one time
• The pathogen is capable of switching expression from one antigen to another
• The pathogen contains a family of variable antigen genes to allow switching

Question 3

How many VSG genes are there in the archive for T. brucei?

Answer 3

Around 1600

Question 4

What is T brucei variant surface glycoprotein (VSG)?

Answer 4

VSG is a glycoprotein that forms a thick protective coat over the surface of T brucei.

Question 5

How is VSG anchored to the parasite cell?

Answer 5

Via a GPI anchor

Question 6

What is the biochemical role of VSG?

Answer 6

It doesn’t appear to have one, beyond acting as a shield

Question 7

How does VSG protect T brucei from adaptive immunity?

Answer 7

It sterically inhibits antibodies form attacking the invariant antigens of the parasite

Question 8

Where does VSG transcription occur?

Answer 8

Bloodstream Expression Sites (BESs)

Question 9

What are BESs?

Answer 9

Specialised regions on the telomeres of T brucei.

Question 10

What polymerase is involved in the transcription of VSG genes?

Answer 10

RNA polymerase I

Question 11

What is the expression site body?

Answer 11

A compartment in the nucleus of T brucei where the individual VSG gene is actively transcribed.
Crucial in ensuring only one VSG gene is expressed at one time (in a single parasite)

Question 12

What are the two mechanisms of switching the expressed surface antigen?

Answer 12

• BES transcription switching
• VSG recombination into the BES

Question 13

What is BES transcription switching?

Answer 13

The active BES is silenced, and a different BES with a new VSG gene is activated

Question 14

What is gene conversion?

Answer 14

A silent VSG gene is copied into the active Bloodstream Expression Site (BES), replacing the currently active VSG gene

Question 15

What is the main route of VSG switching?

Answer 15

Gene conversion
It is a type of homologous recombination that involves copying a silent VSG gene into the expression body site

Question 16

What is the advantage of recombination vs transcription switching?

Answer 16

A compartment in the nucleus of T brucei where the individual VSG gene is actively transcribed.
Crucial in ensuring only one VSG gene is expressed at one time (in a single parasite)