Antigen Presentation & MHC

Question 1

Which cells are the professional antigen presenting cells (APCs)?

Answer 1

macrophages, dendritic cells, B lymphocytes

Question 2

Are mature or immature dendritic cells phagocytic?

Answer 2

Immature DCs are phagocytic; as they mature, they become less phagocytic but more able to present antigen.

Question 3

What is the transporter associated with antigen processing in MHC class I antigen processing?

Answer 3

TAP (function is to shunt antigen from cytosol to ER)

Question 4

Which structures compose the proteasome involved with processing MHC I antigen?

Answer 4

LMP2 and LMP7 (barrel-like structures w/ enzymes that cleave foreign antigen)

Question 5

What do partly folded MHC class I α chains bind to until β2-microglobulin binds?

Answer 5

calnexin (a chaperone)

Question 6

Once MHC class I α:β2m complex is released from calnexin, what happens?

Answer 6

It binds to a complex of chaperone proteins (calreticulin, ERp57) and then binds to TAP via tapasin.

Question 7

What does ERAAP stand for, and what is its purpose?

Answer 7

It stands for ER Aminopeptidase associated w/ Antigen Processing, and it trims N-terminus of peptides in the ER so that they are the correct size to bind tightly to MHC class I molecules.

Question 8

Viral infection stimulates which MHC class?

Answer 8

Class I, causing many MHC molecules to be found on the surface of the antigen presenting cell so they can be loaded with viral antigen and presented to cytotoxic T-cells.

Question 9

What is the difference between MHC class I and class II antigen processing?

Answer 9

• MHC class I is loaded with intracellular antigen that is processed in a proteasome, taken up and delivered into the ER by TAP, and exported to the cell membrane once it binds a peptide.
• MHC class II is loaded with extracellular antigen that is endocytosed in a vesicle, which is acidified and activates proteases to degrade antigen; peptide-containing vesicles fuse w/ vesicles containing MHC class II molecules, and the MHC eventually travels to the cell surface after a series of steps.

Question 10

What is the function of Ii (invariant chain)?

Answer 10

It forms a complex w/ MHC class II molecules and blocks the binding of peptides and misfolded proteins in the ER. This is because MHC class II molecules are supposed to bind extracellular pathogens.

Question 11

Which peptide is bound to MHC class II molecules in the absence of infection?

Answer 11

CLIP (class II associated invariant peptide)

Question 12

What is the molecule responsible for binding to the MHC class II molecule to release CLIP and allow other peptides to bind?

Answer 12

HLA-DM (peptide loader/unloader)

Question 13

True or false: CD4+ T lymphocytes recognize free and soluble antigens.

Answer 13

False - they recognize antigens on the surface of APCs in the context of class II molecules.

Question 14

The CD4 subset of T lymphocytes contain effectors for:

Answer 14

• macrophage activation: Th1

- antibody synthesis: Th2

Question 15

What is required for full activation of a CD4+ T-cell?

Answer 15

It requires interaction of B7 (on APC) with CD28 (on T-cell), along with TCR binding to antigen in the context of MHC class II. This is known as co-stimulation.

Question 16

Which protein is REQUIRED on the surface of the APC in order to allow full activation of the T-cell with clonal expansion?

Answer 16

B7 (if the APC does not already express it, expression must be induced)