A3: Antigen Presentation

Question 1

What is the name of dendritic cells that are located in the skin epidermis?

Answer 1

Langerhans cells

Question 2

What type of dendritic cells are the main producers of type I interferons?

Answer 2

Plasmacytoid dendritic cells

Question 3

What is the difference in function between classical and plasmacytoid dendritic cells?

Answer 3

Classical dendritic cells are mostly found in tissue and function in the induction of T cell responses against most antigens. Plasmacytoid dendritic cells are found in blood and tissue and function in antiviral innate immunity and in T cell response to viruses

Question 4

What are the two ways that dendritic cells respond to microbes?

Answer 4

1) phagocytose/receptor mediated endocytose microbes and display antigens (they function as APCs)
2) microbial products activate toll-like receptors and produce inflammatory cytokines (TNF and IL-1)

Question 5

Which toll-like receptors are expressed on plasmacytoid dendritic cells?

Answer 5

Plasmacytoid dendritic cells are chiefly viral responders, so they express TLR 7 and 9

Question 6

How are dendritic cells attracted to the area where the T cells are?

Answer 6

Once they are activated (via TLR and cytokines) they begin to express CCR7, which then allows them to migrate towards where the T cells are located in the lymph nodes

Question 7

In general, how are internalized antigens processed for display by class II MHC molecules? What about internalized antigens for display by MHC class I?

Answer 7

MHC class II: processed in endosomes and lysosomes
MHC class I: processed in proteasomes (proteolytic structures)

Question 8

What is cross-presentation and how does it work?

Answer 8

Dendritic cells are able to present the antigens of another infected (or dying or tumor) cell to CD8+ cells for killing via cytotoxic death.
Dendritic cells ingest the infected cell and display the antigen on MHC class I

Question 9

Where in the cell do the binding of the MHC molecule with the antigen occur?

Answer 9

For both MHC class I and class II, the binding of the antigen and the MHC molecule occur in the cytosol

Question 10

What are 5 mechanisms where antigen presentation by DC cells can occur?

Answer 10

1. macropinocytosis
2. phagocytosis
3. Fc receptor mediated uptake
4. immune complex uptake
5. receptor mediated endocytosis

Question 11

What is the name of the gene cluster that codes for MHC in humans?

Answer 11

called HLA

Question 12

What genes encode class I MHC molecules? Class II molecules? (in humans)

Answer 12

Class I: HLA-A, B, and C

Class II: HLA-DR, DQ, and DP

Question 13

What are the 3 extracellular binding domains for MHC class I heavy chain? What is the other subunit that binds to the heavy chain?

Answer 13

Alpha 1, alpha 2, and alpha 3 make up the heavy chain. beta2-microglobulin binds to heavy chain

Question 14

What are the two subunit chains for MHC class II? What do these chains bind to?

Answer 14

alpha and beta chains. Bind to the CD4` T cell coreceptor

Question 15

What is the inheritance of MHC molecules? What is another property they have that makes them the key culprit behind organ rejection in transplantation?

Answer 15

They are co-dominantly-expressed and are highly polymorphic so the alleles vary significantly in the population

Question 16

Are the peptide binding clefts on the antigen or on the MHC molecule? What about the anchor residues?

Answer 16

The peptide binding clefts are in the MHC molecules, allowing it to interact with peptides. Anchor residues are residues on peptides that bind with MHC molecules and determine if a peptide will bind

Question 17

What is the main requirement for stable expression of MHC molecules?

Answer 17

They must bind to a peptide!

Question 18

What is the difference between processing of antigens between those antigens that will be displayed on type I MHC and on type II MHC?

Answer 18

Antigens that will be displayed on type I MHC are processed in proteolytic structures (proteasomes).
Antigens that will be displayed on type II MHC are processed in late endosomes and lysosomes.

Question 19

What are the enzymes responsible for generating peptides for class I and for class II MHC?

Answer 19

Class I: proteasome

Class II: cathepsins

Question 20

How are antigens presented on class I MHC?

Answer 20

Viral proteins, phagocytosed microbial proteins, mutated or altered host genes, cell’s misfolded proteins, etc are all targeted for destruction by the ubiquitin-proteasome pathway

Question 21

For MHC class II, how do peptides bind to the MHC?

Answer 21

Newly synthesized MHC have an invariant chain which targets it for late endosomal/lysosomal vesicles that contain the peptide. Once inside, the invariant chain is degraded and the the peptide to be presented is put in its place.

Question 22

For MHC class I, how do peptides bind to MHC?

Answer 22

Peptide is digested in proteasome and must get to MHC near the ER. Done via TAP in the ER membrane. The TAP binds the peptides and pumps them inside of the ER, where they are captured by MHC class I

Question 23

If an antigen is immunodominant, what does that mean?

Answer 23

It means those peptides are preferentially picked up and displayed by MHC molecules and are the ones that the immune system responds to the most

Question 24

Why do vaccines require adjuvant?

Answer 24

The microbial products are presented by dendritic cells which provide the necessary secondary signal for T cell involvement

Question 25

What are the dendritic cells that display antigen to activated B cells?

Answer 25

Follicular dendritic cells. They display antigens coated in antibodies or with complement byproducts C3b and C3d