Lecture 11

Question 1

What are the 4 steps to MHC II presentation via the classical pathway?

Answer 1

1. Synthesis of new MHC II protein
2. generation of the peptides
3. Movement of the MHC class II and invariant chain to MIIC region of the cell, generation of the CLIP peptide
4. Load peptides onto MHC II and move to the surface

Question 2

How is the MHC class II protein synthesized? (step 1)

Answer 2

• alpha and beta chains are transported to the ER and folded by chaperone protein (Ii)
• MHC class II proteins are assembled in the ER and αand βchains, and Ii span the membrane

Question 3

How is it that peptides don’t bind into the cleft of the MHC class II proteins while
it is in the ER?

Answer 3

The Ii binds in the peptide binding groove of MHC class II proteins

Question 4

How do peptides that are displayed on MHC II get into the cell? (step 2)

Answer 4

phagosome/autophagosome forms–>fuse with lysosome–>proteases break down into fragments

Question 5

What is MIIC and how does the peptide get there? How does it make the CLIP peptide? (step 3 MHC II)

Answer 5

• MIIC is a late endosomal compartment; Ii contains sequences that target the new MHC class II proteins to the MIIC compartment
• lysosome protease removes most of the Ii, leaves a small fragment called CLIP

Question 6

How does MHC class II bind the peptide? (step 4)

Answer 6

• HLA-DM mediates the exchange of CLIP for peptide (in the endosome/lysosome)
• HLA-DO regulates HLA-DM

Question 7

How does the MHC class II get to the surface?

Answer 7

HLA-DM dissociates and MHC II folds around the peptide tightly
- it gets transported to cell surface

Question 8

What are the three roles of the invariant chain?

Answer 8

1. assists pairing of alpha and beta chains
2. controls access to MHC peptide binding groove
3. directs MHCIIs to endosomal pathway

Question 9

What are the 4 steps to MHC II presentation via the classical pathway?

Answer 9

1. Synthesis of new MHC I protein
2. Generation of the peptides (either from proteins synthesized by ribosomes or as a result in lysosome degradation)
3. Moving peptides from cytosol to the ER
4. Load peptides onto MHC and move to the surface

Question 10

How is the MHC class I protein synthesized? (step 1)

Answer 10

alpha and b2 genes are transcribed on a ribosome, then the alpha chain is anchored to the membrane of the ER and b2 is soluble
- chaperone protein assists assembly
- Chaperone protein brings MHC to TAP to form PLC

Question 11

How do peptides that are displayed on MHC I get into the cell? (step 2)

Answer 11

proteasome degrades proteins tagged with ubiquitin into peptide fragments, then proteasome trims the peptide

Question 12

How are peptides moved from the cytosol to the ER for MHC I? (step 3)

Answer 12

TAP1/2 transports peptides from the cytosol into the lumen of the ER (bc the peptides are too big to pass through the bilayer)

Question 13

How are the peptides loaded onto MHC I? (step 4)

Answer 13

• TAP delivers the peptide into the MHC binding cleft, ERAP trims the peptide to fit better
• chaperone proteins make sure the PLC doesnt leave until it binds peptide
• ERAD moves all the unwanted peptides back into the cytosol