Antigen Exposure, Processing, and Presentation

Question 1

What inspects antigens presented by MHC class 1?

Answer 1

CD8+ T cells

Question 2

What inspects antigens presented by MHC Class 2?

Answer 2

CD4+ T cell

Question 3

What do CD4+ and CD8+ T cells do in response to seeing an antigen?

Answer 3

CD8+ T cell - kill cell and emit cytokines, CD4+ T cell - emit cytokines

Question 4

2 phases of antigen presenting

Answer 4

Priming and effector phases

Question 5

What is the major basis for transplanted tissue rejection?

Answer 5

MHC incompatibility

Question 6

What presents lipid-based antigens?

Answer 6

CD1

Question 7

Lengths of peptides presented by Class 1a and Class 2 MHCs

Answer 7

Class 1a - 8 to 10 AAs, Class 2 - 13 to 17 AAs

Question 8

What cell recognizes antigens presented by QE?

Answer 8

Regulatory CD8+ T cells, NK cells

Question 9

What classifies type I MHC molecules?

Answer 9

They all bind B2 microglobulin and all have three globular domains and a heavy chain

Question 10

What molecules make up MHC Class 1B?

Answer 10

M3 (mouse), QE, and CD1

Question 11

What peptide fragments that can be presented from antigens?

Answer 11

Proteosomes

Question 12

What type of proteosomes take up ubiquitilated proteins?

Answer 12

Proteosomes with a 19S at either end

Question 13

What proteins act on degraded proteins between the proteosome and delivery to ER?

Answer 13

Cytosolic peptidases

Question 14

How are degraded antigenic peptides delivered from cytosol (post-proteasome) to ER (where MHC will pick them up)?

Answer 14

By active transport via TAP (Transporter of Antigen Peptides

Question 15

Once an antigen fragment arrives in the ER, what cleaves it further?

Answer 15

ERAAP (ER-associated Aminopeptidase)

Question 16

Which end of an antigen fragment can be modified by ERAAP?

Answer 16

Only the N-terminus (the proper C-terminus has to be created in the cytosol before arrival in ER)

Question 17

What happens to antigens that are initially delivered to the ER?

Answer 17

They get retrotranslocated into the cytosol, run through the proteosome, then delivered back to ER

Question 18

What is the difference in the peptide binding groove between Class I and Class II MHC molecules?

Answer 18

Class II has an open ended binding cleft (you dont need peptides of a specific length)

Question 19

Which class of MHC molecules requires antigen degradation before it can present and why?

Answer 19

Class I, because it is not open-ended (theoretically Class II can bind any length antigen)

Question 20

Where do MHC Class II molecules meet their antigens?

Answer 20

In the endosomal/phagosomal compartment

Question 21

Why arent MHC class II proteins degraded with their antigens?

Answer 21

Because MHC is highly resistant to proteases

Question 22

What allows Class II MHC to leave the ER?

Answer 22

Binding of an invariant chain

Question 23

Invariant chain

Answer 23

A 216 AA type II glycoprotein which assembles with Class II MHCs in the ER

Question 24

How do MHC Class IIs and Invariant chains get to the endosome and how do they get separated once they are there?

Answer 24

Invariant chain has a tail sequence which directs the complex to late endosomes. Invariant chain is highly susceptible to proteolysis, but MHC Class II is highly resistant

Question 25

What prevents other peptides from binding MHC Class II before it reaches the endosome?

Answer 25

The CLIP sequence of the invariant chain (which gets separated from the MHC in the endosome)

Question 26

What endosomal protease destroys disulfide bonds?

Answer 26

GILT (gamma-interferon inducible lysosomal thiol reductase)

Question 27

What removes invariant chains CLIP sequence from MHC class II proteins and loads the antigen?

Answer 27

H-2M (mouse) or HLA-DM (man)

Question 28

Why do MHC class Is bind to CD8+ T cells and Class IIs to CD4+ T cells and where on each MHC does the relevant receptor attach?

Answer 28

Class Is have CD8 receptors on their A3 domain, Class IIs have CD4 receptors on their B2 domain

Question 29

What types of cells express MHC class I?

Answer 29

All cells except RBCs (but low expression on hepatocytes, kidney, and brain)

Question 30

Which MHC class is expressed in more cell types?

Answer 30

MHC Class I. Class II is mainly dendritic cells, macrophages, and B cells (overactivation can be a problem)

Question 31

Dendritic cells

Answer 31

Take up material non-specifically at sites of inflammation by macropinocytosis and then migrate to lymph nodes and spleen for presentation to T cells

Question 32

Macrophages

Answer 32

Harbor intracellular organisms, presentation to T cells results in release of factors that activate the macrophage

Question 33

What causes cells to express Class II MHCs during an immune response

Answer 33

Gamma-interferon

Question 34

What type of cell can undergo cross-presentation and what does this mean?

Answer 34

Dendritic cells. This is where they phagocytose an infected cell so their own MHC Class I can get access to antigen to present (antigen has to enter DCs cytosol)

Question 35

Why is cross-presentation especially useful?

Answer 35

Because many pathogens have developed strategies for inhibiting class I processing, but DC cross-presentation escapes such inhibition

Question 36

What are the loci of the MHC class II gene in humans and which one has the most variability?

Answer 36

DP, DQ, DR (DR is most variable)

Question 37

Superantigens

Answer 37

Cause non-specific activation of a huge number of T-cells

Question 38

What are the three professional Antigen Presenting Cells (APCs) and what MHC class do they always use?

Answer 38

Dendritic cell, Macrophage, and B cell. Always use Class II

Question 39

What conformations of antigen do B cells and T cells respectively react to?

Answer 39

B cells - native, folded antigen, T-cells - antigen fragments

Question 40

How is the T-cell response to mycobacterial infection different?

Answer 40

In mycobacterial infections, parasitized macrophages present pathogen-derived peptides to CD4+ T-cells (not CD8+), which incite them to carry out more efficient killing of pathogen

Question 41

Which MHC class can present superantigens?

Answer 41

Class II only

Question 42

What polypeptide chains compose MHC Class I molecules?

Answer 42

Heavy chain (A1, A2, A3 plus transmembrane domain and tail), and B2-microglobulin (one IG-like domain non-covalently associated with the heavy chain)

Question 43

Where is the peptide binding groove on MHC class 1 molecules?

Answer 43

At the interface between the A1 and A2 domains

Question 44

Is the antigen presenting system quiet in uninfected cells?

Answer 44

No, it is constitutively active. For uninfected cells, it is presenting normal improperly folded proteins or those that are turned over as part of normal upkeep

Question 45

What polypeptide chains compose MHC Class 2 molecules?

Answer 45

Alpha and B (each roughly same size with transmembrane portions)

Question 46

Where is the peptide binding groove in MHC Class 2 molecules?

Answer 46

Between the A1 and B1 domains

Question 47

What type of antigen cannot be readily absorbed by dendritic cells via cross-presentation?

Answer 47

Soluble antigens

Question 48

What is another name for MHC in humans?

Answer 48

Human Leukocyte Antigen

Question 49

How many class I heavy chain genes does each person have?

Answer 49

6. Three (A,B,C) on each chromosome

Question 50

How many different MHC class II molecules can be expressed and how many alleles are these from?

Answer 50

12 different MHC class II molecules from 3 alleles (HLA-DP, HLA-DQ, HLA-DR)

Question 51

Also encoded in the MHC Class 2 region of the genome are genes for what?

Answer 51

TAP and two proteasomal subunits

Question 52

In what part of the MHC molecule is most variation found (within the population)?

Answer 52

In the peptide binding pocket region

Question 53

Which MHC class alleles have a stronger link with autoimmune diseases?

Answer 53

Class II

Question 54

What molecules bind superantigens and where do they bind?

Answer 54

Superantigens bind to the outside of MHC Class II molecules

Question 55

What does HLA-E activate, what does it bind, and what type of MHC is it?

Answer 55

MHC Class 1b, activates CD8+ T cells and NK cells, binds B2M and peptides from bacterially-derived HSPs

Question 56

What is CD1 and what does it respond to?

Answer 56

A non-MHC-encoded molecule which presents mycolic acid and lipoarabinomannan (cell wall components) from Mycobacteria