Lecture 8

Question 1

How many signals do T cells need to get activated? Name them.

Answer 1

1. TCR-peptide+MHC
2. Costimulation: CD28-B7
3. Cytokine

Question 2

How do dendritic cells change with PAMP binding?

Answer 2

↑MHC 1 AND2
↑B7 = costimulatory molecule
Change chemokine receptors to move toward lymph node for T/B cell stimulation
From phagocytosis role –> processing machine

Question 3

Do APCs always express costimulatory molecules?

Answer 3

NO - must undergo maturation to express these
DC & macrophages ↑costim molecules after binding PAMPs, getting proinflam cytokines of CD40-CD40L
B cells must be induced by T cells via CD40-CD40L

Question 4

Do all T cells require co-stimulation?

Answer 4

NO
Naive - always
Memory - sometimes
Effector - no

Question 5

What are plasmacytoid DCs?

Answer 5

Innate immunity

Make a lot of type IFNs when activated

Question 6

What are fDCs?

Answer 6

@ secondary lymph organs
Not - MHC restricted
Display antigen to B cells

Question 7

What are CD8+ DC cells?

Answer 7

DC cells that can express MHC1

Question 8

Which has higher precursor frequency: pathogens or non-self MHC?

Answer 8

Non-self MHC = higher precursor frequency

Question 9

For MHC2, which chains are MHC encoded - alpha or beta?

Answer 9

BOTH

Question 10

For MHC1, which chains are MHC encoded? Alpha or beta2 microglobuin?

Answer 10

Alpha aka the heavy chain ONLY

Question 11

What are superantigens?

Answer 11

Creates peptide non-specific TCR/MHC interactions

General T cell activation - cytokines aren’t antigen specific = non-specific inflammation

Question 12

What 5 molecules are critical for MHC1 antigen processing?

Answer 12

1. Chaperones = calnexin, calreticulin
2. Tapasin - holds MHC 1 near TAP
3. TAP brings in peptides
4. Proteosome - unique to MHC1!
5. ERAAP - customizes peptides for the specific MHC

Question 13

Describe the proteosome used for MHC1 peptide presentation.

Answer 13

20s core
Alpha & beta subunits = proteolytic
C term creates peptides that are more likely to bind MHC 1 molecules
Fxn upregulated by IFN gamma
- + PA28 cap to speed up peptide production

Question 14

What is the source of protein antigens for MHC 1 vs 2?

Answer 14

1: Sometime phagosomes but usually proteins in the cytosol
2: Endosomal/lysosomal proteins internalized from extracellular environment

Question 15

What is cross priming?

Answer 15

CD8 DCs!!!!!
The ability of APCs to present on MHC1s
TAP dependent
B/C NEED COSTIM

Question 16

What is alloreactivity?

Answer 16

Reaction to non-self MHC
Think of transplant
MHCa + MHCa - identical match vs small DNA differences due to polymorphisms

Question 17

Which viruses block peptide entry into the ER to evade immune response?

Answer 17

Herpes simplex 1
Human cytomegalovirus
Bovine herpes

Question 18

Which viruses retain MHC1 in the ER to evade immune response?

Answer 18

Adenovirus
Human cytomegalovirus
Murine “ “

Question 19

Which viruses degrade MHC 1 to evade immune response?

Answer 19

Human cytomegalovirus

Murine gamma herpes

Question 20

What virus binds MHC 1 at cell surface to evade immune response?

Answer 20

Murine cytomegalovirus

Question 21

How can you increase avidity?

Answer 21

Tetramer of MHC-peptide with TCR

Question 22

Why would you have a MHC2 deficiency? What is the net effect?

Answer 22

Lacking TFs
NO CD4 cells
EX: Coeliac

Question 23

Why would you have a MHC1 deficiency? What is the net effect?

Answer 23

TAP mutation
Beta2 microglobulin mutation
NO CD8 cells

Question 24

Why do we care about peptide anchor residues?

Answer 24

Predict which peptides will bind well to particular MHC alleles

• Vaccination
• Looking for antigen-specific T cells
• Tumor immunology