6. antigen processing and presentation

Question 1

why do t cells need antigen presentation?

Answer 1

unlike b cells, t cells cannot recognise native antigen

Question 2

how are t cells activated?

Answer 2

antigen presenting cells (APCs) determine which peptides will be presented on class I and class II MHC during initial activation 
t cells must distinguish between external and internal antigens

Question 3

what is antigen processing?

Answer 3

enzymatic process of degrading proteins through proteases into antigenic peptides
requires energy and movement of endocytic vesicles

Question 4

antigen processing pathways

Answer 4

endogenous antigens pathway - antigens in cytosol presented on MHC class I molecules to CD8+ t cells
exogenous antigens pathway  - antigens in endoscopes presented on class II MHC molecules CD4+ t cells

Question 5

endogenous antigens

Answer 5

from proteins produced inside the cell

includes self protein antigens and foreign protein antigens

Question 6

how does the endogenous antigen pathway work?

Answer 6

antigen is intracellular  
proteasome breaks it down into peptides 
peptides are transported to t he endoplasmic reticulum  
peptide binds there too MHC class I 
MHC class I presents peptide at cell surface

Question 7

what do endogenous antigen proteasome do?

Answer 7

proteasome unfolds proteins then cleaves proteins into peptides and amino acids

Question 8

what are TAP proteins?

Answer 8

transporters associated with antigen processing
TAP 1 and TAP2 form heterodimer in membrane of ER
facilitates transport of peptides from cytoplasm into lumen of ER
preferentially transports peptides with 8-15 amino acids

Question 9

cd8+ t cytotoxic cell

Answer 9

CTLs
activated by endogenous or intracellular antigens
primarily needed for the eradication of infected cells
can be activated against cancer cells (target neo antigens)

Question 10

CTL killing of infected cells

Answer 10

viruses replicate inside cells -+ many bacteria and parasites live inside cells
antigens for stimulating CTLs come from inside the cell as they signal an intracellular infection

Question 11

MHC class I immune evasion

Answer 11

viruses can interfere with class I MHC expression to escape being killed 
herpes simplex virus - protein selectively binds to TAP, inhibiting transfer of peptides into ER

Question 12

exogenous antigen pathway

Answer 12

antigen  is taken into intracellular vesicles  
acidification of vesicles activates proteases to degrade antigen into peptide fragments 
vesicles with peptide  fragments fuse with vesicles containing class II MHC molecules 
peptide fragments are loaded onto MHC

Question 13

what happens to class II MHC molecules?

Answer 13

MHC class II alpha and beta chains associate in the ER
invariant chain blocks peptide binding in the ER
in trans golgi network, MHC
isolated into vesicles
invariant chain is cleaned, leaving CLIP fragment
vesicles deliver MHC to endocytic vesicles
HLA-DM facilitates release of CLIP, so peptides can bind

Question 14

CD4+ helper t cells

Answer 14

activated by exogenous antigens
foreign antigens must be taken up by antigen presenting cells
leads to activation of macrophages and production of secreted antibody by plasma cells

Question 15

MHC class II immune evasion

Answer 15

viral inhibition
adenovirus interferes with class II upregulation
HSV viral envelope protein (glycoprotein B) reduces MHC processing and inhibits production of invariant chain peptide
HIV interferes with class II processing
leishmania and mycobacteria prevent phagosome-lysosome fusion

Question 16

how are T cells kept apart?

Answer 16

both classes  traverse through ER to cell surface 
control is through accessory proteins 
class I requries TAP, tapsasin, 
class II requires low pH