Antigen Processing and Presentation

Question 1

Describe processing & presentation of exogenous Ag and explain the consequences.

Answer 1

1. Ag degraded by proteasome
2. Resulting peptides are translocated via transporter associated with Ag presentation (TAP) into ER lumen and loaded onto MHC class I molecules
3. Peptide-MHC class I complexes are released from the ER and transported via the Golgi to the plasma membrane for Ag presentation to CD8 T cells

Question 2

What is the purpose of antigen presentation?

Answer 2

1. Educate the immune system and the discrimination of self versus non-self (foreign) Ag
2. Through Ag presentation, cells display their proteome on their cell surface providing information of a cell’s health
3. THUS - Ag presentation is essential for not only pathogen-specific immune response but also immune tolerance

Question 3

What is an antigen?

Answer 3

Any substance that can be recognized by the antigen receptor of a B cell or by the T cell receptor when complex with MHC molecules

Question 4

How do B cells see Ag?

Answer 4

Directly via BCR (slg)

B cells detect native (unprocessed) Ag

Question 5

How do T cells see Ag?

Answer 5

T cells interact with Ag complexed with MHC (Major histocompatability complex)

Question 6

How do T cell receptor interact with peptide-MHC molecule?

Answer 6

1. T cell receptor interacts with peptide and the presenting MHC molecule
2. Different MHC molecules present different peptides based on the peptides that fit and stable within MHC groove
3. Strength of interaction determines type of response

Question 7

What is the difference in length of MHC class I and class II?

Answer 7

Class I - 8-10 aa
Class 2 - 15-24 aa

Question 8

What are the roles of Ag presentation in health and disease? Which roles if awry, cause autoimmunity?

Answer 8

1. Transplantation
2. Central tolerance - dvlping T cells
3. Peripheral tolerance - mature T cells
4. Pathogen immunity
5. Tumour immunity

Central tolerance and peripheral tolerance

Question 9

What are the three ways an immature T cell can develop into?

Answer 9

1. Death by neglect
2. +ve selection of conventional T cells
3. -ve selection of autoreactive T cells

Question 10

What recognizes MHC class I?

Answer 10

CD8 cytotoxic T cells

Question 11

What recognizes MHC class II?

Answer 11

CD4 helper T cells

Question 12

Compare professional and non-professional APCs.

Answer 12

Non-professional APCs include all nucleated cell types in the body

Professional APCs = DCs, Macrophages, B cells
- Present Ag with MHC class I and MHC II molecules
- DCs are especially equipped to activate naive T cells

Question 13

What are the two ways extracellular Ag can be uptaken for the presentation by MHC class II molecules?

Answer 13

1. Ag uptake via B cell receptor
2. Ag uptake by PRRs, C type lectin receptors, Fc receptors, scavenger receptors, constant sampling

Question 14

Describe processing & presentation of MHC class II and explain the consequences

Answer 14

1. MHC class II a- and b-chains assemble in the ER and form a complex with the invariant chain (Ii).
2. Ii-MHC class II heterotrimer is transported through the Golgi to the MHC class II compartment (MIIC).
3. Endocytosed proteins and Ii are degraded by resident proteases in the MIIC
4. The class II-associated Ii peptide (CLIP) fragment of Ii remains in the peptide-binding groove of the MHC class II dimer and is exchanged for an antigenic peptide with the help of the dedicated chaperone HLA-DM
5. MHC Class II molecules are then transported to the plasma membrane for recognition by CD4 T cells

Question 15

What is cross-presentation/cross-priming essential for?

Answer 15

1. Allows CD8 T cells to see exogenous Ag
   - Cross-priming enables extracellular Ag to be presented to CD8 T cells
2. Critical for immunity against most tumours & some viruses

Question 16

Compare the 3 types of professional APCs.

Answer 16

Dendritic cell:
Ag uptake & recognition - constant sampling PRRs
Costimulatory activity - +++
T-cell activation - naive, effector and memory T cells
Importance - crucial to launch T cell adaptive response

Macrophage:
Ag uptake & recognition - non-specific PRRs
Costimulatory activity - ++
T-cell activation - effector & memory
Importance - re-stimulates effector Th in tissues

B cell:
Ag uptake & recognition -
Costimulatory activity
T-cell activation
Importance

Question 18

When does antigen stimulation under non-inflammatory conditions happen?

Answer 18

1. Lack of co-stimulatory molecules
2. Lack of inflammatory cytokines
   TOLERANCE

Question 19

What happens during antigen stimulation under inflammatory conditions?

Answer 19

1. Increased co-stimulatory molecule expression
2. Increased inflammatory cytokine production
   IMMUNITY

Question 20

What happens to T cells when they get activated?

Answer 20

Naive T cell (day 0) ➔ effector T cell (day 8) ➔ memory t cell (>day 40) or apoptosis

Question 21

Where are naive T cells found?

Answer 21

Lymph, blood

Question 22

Where are effector and memory T cells found?

Answer 22

lymph, blood and tissues

Question 23

What is the lifespan of the different types of T cells? (From shortest to longest)

Answer 23

effector < naive < memory

Question 24

How do B cells differentiate?

Answer 24

B cell ➔ effector cell ➔ plasma cell

Question 25

What is the function of activated effector CD4 Th cells?

Answer 25

1. Promote Ab response
2. Help activate other cell types through secretion of cytokines (B cells, CTL, etc.)

Question 26

What is the function of effector CD8 T cells?

Answer 26

Lyse target cells in Ag-dependent manner?