Antigen Presentation and the MHC

Question 1

What differentiates B cells from other APCs?

Answer 1

They are not phagocytic

Question 2

What are macrophages in the liver called?

Answer 2

Kupffer cells

Question 3

What are macrophages in the brain called?

Answer 3

Microglial cells

Question 4

What are APCs in the skin called?

Answer 4

Langerhans’ cells

Question 5

What happens to Langerhans cells from the skin when they encounter a pathogen?

Answer 5

They travel through the afferent lymphatics into a draining lymph node and migrate to the paracortex where they can then present antigen to T lymphocytes

Question 6

Where are follicular dendritic cells found? What is their purpose?

Answer 6

They are found in B lymphocyte areas of lymph nodes and spleens.

They present antigen to B lymphocytes

Question 7

What are the two distinct lineages of dendritic cells?

Answer 7

Conventional and plasmacytoid

Question 8

What are plasmacytoid dendritic cells important for?

Answer 8

Protection against viruses. They produce large quantities of interferon in response to viral infections.

Question 9

What happens to conventional dendritic cells as they mature?

Answer 9

They downregulate their phagocytic functions and upregulate their antigen presentation

Question 10

When is B lymphocyte antigen presentation the most important?

Answer 10

During a secondary antibody response

Question 11

Briefly describe the antigen presentation process by class I MHC.

Answer 11

1) Virus infects a cell
2) Viral proteins are synthesized in the cytosol
3) Peptide fragments of viral proteins are bound by class I MHC in the ER
4) Bound peptides are transported by MHC Class I to the cell surface where they can be displayed to T-lymphocytes

Question 12

Briefly describe the antigen presentation process by class II MHC.

Answer 12

1) Antigen is take up from the extracellular space by endocytosis (macrophage) or receptor-mediated endocytosis (B-cells)
2) Acidification of maturing endosome activates proteases to degrade antigen into peptide fragments
3) Vesicles containing peptides fuse with vesicles containing class II MHC
4) Invariant chain forms a complex with MHC class II blocking binding of peptides and misfolded proteins
5) Invariant chain is cleaved leaving CLIP in the peptide binding groove
6) HLA-DM binds to class II molecule, releasing CLPI and allowing peptides to bind.
7) Presentation at cell surface

Question 13

How are viral proteins degraded so that they can be presented by class I MHC?

Answer 13

Host cell’s proteasome (comprised of subunits LMP2 and LMP7)

Question 14

What is the role of TAP-1 and TAP-2?

Answer 14

TAP: Transporters Associated with Antigen Processing)- transport peptides generated in the cytosol to the endoplasmic reticulum

Question 15

Name three chaperone proteins that allows newly synthesized MHC Class I (alpha and Beta2 microglobulin) to assemble in the ER?

Answer 15

Calnexin, Erp57 and calreticulin

Question 16

What is the role of ERAAP in MHC class I assembly?

Answer 16

ERAAP (endoplasmic reticulum aminopeptidase associated with antigen processing)- trims the protein fragments to the right length (9 amino acids) so that they can bind to MHC Class I. Following binding, the Ag/MHC class I complex can leave the ER, travel through the golgi, and be transported to the cell surface for presentation to CD8+ cytotoxic T cells.

Question 17

Peptides that bind to MHC Class II molecules are generated where?

Answer 17

In the acidified endocytic vesicles

Question 18

Where are class II MHC molecules synthesized?

Answer 18

Class II are synthesized in the ER.

Question 19

What is the role of the invariant chain?

Answer 19

The invariant chain is synthesized along with class II MHC in the ER, and blocks the binding of peptides and misfolded proteins

Question 20

How is the invariant chain cleaved so that Ag can bind to class II MHC?

Answer 20

The invariant chain is cleaved in an acidified endosome., leaving a short peptide fragment, CLIP, still bound to class II molecules.

Question 21

How is the CLIP protein eventually displaced from the binding site of class II MHC?

Answer 21

HLA-DM binds to the molecule releasing CLIP and allowing other peptides to bind. The MHC class II molecule can then travel to the cell surface to be displayed.

Question 22

What HLA-DM?

Answer 22

CLIP unloader/loader

Question 23

Differentiate what is the peptide binding grooves of class I and class II under normal conditions (no infection)

Answer 23

Class I: normal self-peptide

Class II: CLIP

Question 24

Can class I and class II be in the same cell at the same time?

Answer 24

Yes- they are in APCs (macrophages, dendritic cells and B-cells)

Question 25

Differentiate the role of Th1 vs Th2 cells

Answer 25

Th1: activates macrophages (increases phagocytic activity)

Th2: activates B-cells (promotes growth and differentiation)

Question 26

What co-stimulatory molecule is expressed on the surface of mature dendritic cells?

Answer 26

B7

Question 27

Activation of naive T cells by antigen requires what two signals?

Answer 27

1) Presentation of peptide by MHC

2) Interaction between B7 on the APC and CD28 on the membrane of the T cell

Question 28

The B7 co-stimulatory molecule on APCs binds to what on the T cell?

Answer 28

CD28

Question 29

T cells that recognize peptides expressed by MHC class II on the surface of the APC are stimulated to express what ligand? What does it bind to?

Answer 29

CD40 ligand.

Binds to CD40, which is normally expressed on the APC.

Question 30

What does binding of CD40L to CD40 induce?

Answer 30

B7 expression by the APC, which can now bind to CD28 on the T cell

Question 31

Do B cells secrete antibody in the absence of T cells?

Answer 31

No- production of antibody to most antigens requires not just B cells but also T cells.

Question 32

How does T cell activation of B cells work?

Answer 32

B cells take up antigen, then B cells process the antigen and display them via class II MHC to T cells. This process activates B-cells to produce B7, which co-stimulates CD28 on the T cell, and activates the naive T cell.

This activation of the T cell induces expression of CD40L, which engages CD40 on the B-cell, activating the T cell to produce cytokines, and allowing the B-cell to inyo plasma cells that secrete antibody.

Question 33

Differentiate the activation of T cells vs the activation of B-cells (in terms of cytokines/ligand binding)

Answer 33

1) T cells require 2 signals (B7 and MHC/peptide), both ligand binding interactions
2) B cells are activated by cytokines produced by activated T cells

Question 34

What is the immunological synapse?

Answer 34

Mechanism of sustained TCR engagement- a form of specialized contact

The mature immunological synapse is defined by a specific pattern of receptor segregation with a central cluster of TCRs surrounded by a ring of adhesion molecules (like LFA-1)

Question 35

T helper 1 cells are classically thought to activate macrophages to become more phagocytic. Can Th1 cells also activate B-cells to produce antibodies?

Answer 35

Yes, but to a lesser extent than Th2 cells.