Week 7 Reading Chapter 6 124-134

Question 1

What types of peptides are loaded onto MHC I

Answer 1

Cytosolic peptides are loaded onto MHC I and recognized by CD8+, while extracellular peptides that are uptaken are recognized by MHC II and recognized by CD4+

Question 2

How does Interferon gamma improve MHC presentation?

Answer 2

Interferon mediates the conversion of the constitutive proteasome to the immunoproteasome (changes beta chain to LMP2, LMP7, MECL-1); also increases the rate at which MHC molecules are transcribed.

Question 3

TAP

Answer 3

Dimeric protein that is responsible for the transport of peptides from the cytosol into the ER; ATP dependent;

Question 4

Tapasin

Answer 4

located in the ER; binds to TAP and MHC I and brings them together. Aids in peptide loading; once peptide is bound tapasin dissociates

Question 5

What chaperone proteins are responsible for the folding and stability of MHC I a chain?

Answer 5

Calnexin (also responsible for folding and assembly of MHC II) and calreticulin.

Question 6

ERAP

Answer 6

ER resident aminopeptidase; further trims peptides to fit into MHC I binding cleft

Question 7

What are the two reasons Class II MHC is not loaded with peptides while they are in the ER?

Answer 7

1) because they do not associate with TAP 2) Because invariant chain blocks peptide binding.

Question 8

What cell types uptake extracellular pathogens for loading on MHC II?

Answer 8

DCs, macrophages, B Cells

Question 9

Invariant chain

Answer 9

Ii; promotes folding and assembly of Class II MHC molecules to the late endosomes and lysosomes; blocks peptide binding cleft

Question 10

What enzymes mediate the removal of Ii from MHC II?

Answer 10

Cathepsins and HLA-DM

Question 11

CLIP

Answer 11

Class II associated invariant chain peptide; remnant of Ii post proteolytic cleavage of Ii; blocks antigen binding

Question 12

HLA-DM

Answer 12

MHC encoded enzyme responsible for the removal of CLIP; adds other peptides to MHC II; tests for the highest affinity peptide

Question 13

Cross presentation

Answer 13

Exception!!: some DCs have the ability to capture an to ingest virus infected or tumor cells and present viral or tumor antigens to naive CD8+ T lymphocytes; phagosomes fuse with ER; proteins are translocated from ER to cytosol

Question 14

Autophagy

Answer 14

Exception!! cytosolic proteins are trapped within membrane bound vesicles (autophagosomes) vesicles fuse with lysosomes; available for presentation by Class II MHC.