Antigen Presentation and Dendritic Cells

Question 1

What is the difference between B and T cell antigen recognition?

Answer 1

B cells recognise whole intact antigen via surface Ig
T cells recognise processed and degraded antigen presented in MHC via surface TCR
- Class II MHC for CD4
- Class I MHC for CD8
(T cells can’t respond unless the antigen has been properly processed!)

Question 2

How is antigen processed generally (both MHC I and MHCII)?

Answer 2

antigen is broken into peptides
peptides are transported to the ER
MHC molecules are synthesized in the ER and bind peptides in their groove
different MHC are able to bind different peptide sets (and ability to bind is inherited)

Question 3

How is antigen processed via the MHC I pathway?

Answer 3

cytoplasmic peptides are degraded by a proteosome (expressed in all cells)
free peptides are transported to the ER by specific transporters (TAP-1 and TAP-2)
peptides associate with and stabilise an MHC Class I molecule
complex is transferred to the cell surface and expressed by the Golgi apparatus (for recognition by T cell)

Question 4

How is antigen processed via the MHC II pathway (APC degradation pathway)?

Answer 4

MHC is synthesised in the RER
moves to trans Golgi network
bound to CLIP to prevent premature binding
Antigen is taken up from the extracellular space (phagocytosed) into intacellular vesicles
acidfication of the vesicel activates the proteases to degrade the antigen into fragments
vesicle containing peptides, fuses with a vesicle containing MHC class II molecules
peptides replace CLIP
transported to the cell surface for expression

Question 5

How do some viruses subvert the antigen presentation pathway?

• HSV
• adenovirus
• CMV

Answer 5

HSV: produces a TAP inhibitor protein (prevent transport of peptides onto MHC
Adenovirus: produces a protein that anchors MHC in the ER
CMV: accelerates protein transport out of the ER (reduces chances of binding to MHC)

Question 6

What are the mechanisms of cross presentation in APCs for? (retrograde translocation, autophagy)

Answer 6

necessary to allow CD8 response to engulfed proteins (external antigen) and CD4 response to cytosolic proteins
Retrograde translocation
- proteins transported back to the cytosol from the endocytic vesicle, processed by proteosome and presented on MHC I
Autophagy
- cytosolic antigens aretrafficked along the MHC II pathway for CD4 response (self proteins for tolerance, cytosolic pathogens eg EBV)

Question 7

Where are APCs generally found?

Answer 7

Sentinels in the tissues

• epidermis and mucosa as Langerhan cells
• dermis
• interstitia of vascularised organs
• migrate to lymphoid tissue once activated

Question 8

What is the role of dendritic cells in the immune system?

Answer 8

• initiate immune response (activate naive and memory T and B cells)
• Role in T cell tolerance (immature DCs lack co-stimulatory molecules, tolerise T cells)
• capture, process and present antigen
  highly express MHC and accessory molecules

Question 9

What is the effect on the dendritic cell of becoming activated?

Answer 9

Travels to the lypmhoid tissue (LNs, spleen)
Enters into T cell areas
Upregulation of antigen presenting and co-strimulating molecules
Production of cytokines: IL-12, TNF, IL-10, IL-6, IFN type I
recruit DC precursors to the periphery, increase DC survival (irreversible maturation followed by apoptotic death)