Antigen presentation

Question 1

Types of APCs

Answer 1

• Dendritic cells (“professional” APCs)
• Macrophages
• B cells

Question 2

Immature vs Mature dendritic cells

Answer 2

• Immature:
  
  • round shape
  • high endocytic capacity
  • low expression of co-stimulatory molecules
• Mature:
  
  • develop longer dendrites (finger-like projections)
  • high APC capacity
  • high expression of co-stimulatory molecules

Question 3

MHC I vs MHC II

Answer 3

Note: MHC in mice = HLA in humans

• MHC I
  
  • Expressed on all nucleated cells
  • Recognised by CD8+ T cells
  • Presents peptides of 8-10 AAs
  • Presents Ag from inside cell
• MHC II
  
  • Binds larged peptides - 14-20 AAs long
  • Recognised by CD4+ T cells
  • presents Ag from outside cell

Question 4

CD4+ T helper cells recognised antigen presented by:

Answer 4

MHC II

Question 5

CD8+ T cells recognise antigen presented by:

Answer 5

MHC I

Question 6

Describe the process by which peptides are generated and
loaded onto MHC-I.

Answer 6

Endogenous pathway for Ag presentation:

1. Proteasome degrades protein (Ag) to peptides and releases them into the cytosol
2. TAP transports SHORT (8-10 AAs) peptides from the cytosol to lumen of the ER
3. In the ER, TAP proteins load peptides onto MHC I via tapasin
4. Peptide-bound MHC I leaves the ER — exported to the cell membrane
5. MHC I presented to circulating CD8 T cells (& NK cells)

Question 7

Exogenous pathway of antigen processing & presentation

Answer 7

1. APC (e.g. dendritic cell) ingests exogenous Ag through endocytosis
2. Acidification degrades Ag into peptides (14-20 AAs long)
3. Invariant chain temporarily forms complex with MHC II molecule - prevents premature binding of peptides in the ER to MHC II by occupying its binding groove
4. Vesicle containing the complex leaves ER
5. Invariant chain is cleaved (due to vesicle acidification - proteases activated), leaving a short peptide fragment, CLIP, still occupying the binding groove
6. Vesicles containing peptides fuse with vesicles containing MHC II molecules - Peptides can’t yet bind due to CLIP
7. HLA-DM binds to MHC II, releasing CLIP & allowing the peptides to bind to MHC II
8. Peptide-bound MHC II then travels to cell surface for presentation to CD4+ T cells

Question 8

What type of peptides are presented by MHC II to CD4+ T cells

Answer 8

Endocytosed proteins (peptides)

Question 9

What type of peptides are presented by MHC II to CD8+ T cells

Answer 9

Cytosolic proteins (peptides)

Question 10

CD4 T cells vs CD8 T cells - Biology/Function

Answer 10

• CD4 T cells are “helper” cells (Th cells)
  
  • They produce cytokines:
    
    • IL-4 helps B cells make antibodies
    • TRAIL helps CD8 T cells be cytotoxic
• CD8 T cells are “cytotoxic” cells (CTL)
  
  • They produce cytokines:
    
    • TNF and IFN-gamma —> directly anti-viral

Question 11

How do viral antigens mutate

Answer 11

Either:
* Antigenic drift - mistakes make during DNA replication produces virus with new antigenic variants (slightly different strain)

• Antigenic shift - Viral genetic material is exchanged between TWO different virus strains during replication –> may be capable of cross-species transmission