Antigen Processing and Presentation

Question 1

Describe where cytosolic pathogens are degraded, bound, presented and the effect from successful binding.

Answer 1

Degraded: cytosol
Bound: MHC class I
Presented: CD8 cytotoxic T-cells
Effect: cell death (apoptosis)

Question 2

Describe where extracellular pathogens are degraded, bound, presented and the effect of successful binding.

Answer 2

Degraded: endocytic vesicles (endosome, lysosome. phagosome)
Bound: MHC class II
Presented: CD4+ helper T-cells
Effect: activation of B-cells

Question 3

What occurs in the secretory pathway?

Answer 3

• Proteins are synthesized in the RER
• distributed to cell surface, lysosomes, or secreted.

Question 4

Describe the proteins of the exocytic pathway.

Answer 4

• proteins and ligands are brought into cell via budding vesicles
• once inside cell the proteins are receptor-mediated, phagocytized, autophagy

Question 5

How are the levels of proteins inside a cell regulated?

Answer 5

1. proteasomes
2. more translation

Question 6

Peptides that bind to MHC I in the endogenous pathway are generated by:

Answer 6

proteasomes

Question 7

What tags proteins for degradation by proteasomes?

Answer 7

ubiquitin

Question 8

Where are peptides transported after degradation in the cytosol in the endogenous pathway?

Answer 8

RER

Question 9

MHC class I is synthesized by ribosomes in the:
A. RER
B. Golgi
C. Lysosome
D. TAP

Answer 9

A. RER

Question 10

Which molecules facilitate the movement of peptides from the cytosol to the lumen of RER?

Answer 10

TAP

Question 11

Which chaperone proteins aid in MHC class I assembly?

Answer 11

1. Tapasin: brings MHC I close to TAP
2. ERAP: trims peptides to 8-10 amino acids in length

Question 12

In the exogenous pathway, how do extracellular pathogens gain access to vesicles?

Answer 12

• endocytosis
• phagocytosis
• autophagy

Question 13

What prevents peptides from binding to MHC class II groove too early in the RER?

Answer 13

invariant chain (Ii)

Question 14

The function of CLIP is:
A. degrades HLA-DM
B. degrades peptide for binding
C. degrades invariant chain

Answer 14

C. degrades invariant chain

Question 15

Once the invariant chain is degraded by CLIP, what occurs next?

Answer 15

HLA-DM exchanges out clip and replaces it with peptide fragment

Question 16

Explain the steps of the endogenous pathway.

Answer 16

1. Intracellular pathogens-proteins or self-proteins from cytosol are tagged with ubiquitin. Proteosome enzyme cleaves tagged proteins. These proteins are transported to the R.E.R.
2. TAP proteins transport tagged proteins to the lumen of the R.E.R. MHCI molecules are synthesized by R.E.R. ribosomes. MHCI expression includes an α chain associated with a peptide fragment from cytosol and β2 microglobulin. ERAP ensures that the peptide fragments are 8-10 amino acids in length
3. MHCI goes through secretory pathway. The vesicle buds from the R.E.R. to the Golgi. From the Golgi the vesicle with MHCI is transported to the cell surface.
4. CD8+ coreceptor on TCRs recognize intracellular antigen-degraded peptides bound to MHCI on cytotoxic T-cells. Expressed on all nucleated cells.

Question 17

Explain the steps of the exogenous pathway.

Answer 17

1. MHCII molecules are produced by ribosomes in the R.E.R. The invariant chain on the MHCII molecules blocks binding site do it does not get loaded w/ endogenous peptide fragments
2. Extracellular antigens are phagocytized or internalized in endocytic vesicles. Proteins in the early endosomes are degraded into peptide fragments. This vesicle fuses with the MHCII vesicle.
3. Ii is initially degraded but the left over fragment present on MHCII is CLIP.
4. HLA-DM exchanges CLIP from groove and replaces it with exogenous peptide fragment in the MHCII late endosome.
5. CD4+ coreceptor on TCRs recognize extracellular antigen-degraded peptides bound to MHCII on T helper cells.