Antigen Presentation (Ch 3)

Question 1

MHC Class I Structure and Location

Answer 1

• On all nucleated cells
• Alpha chain + beta2-microglobulin
• Alpha chain has 3 extracellular domains
  
  • Alpha 1 and alpha 2 - peptide binding cleft; floor is where peptide binds via anchoring residues and walls make contact w/ T cell receptor
  • Alpha 3- invariant; binds CD8+ co-receptor
    
    • ***So CD8+ T cells can only respond to Class I MHC

Question 2

MHC Class II Structure and Location

Answer 2

• On dendritic cells, macrophages and B cells (APCs)
• alpha and beta transmembrane chains; ea chain has 2 extracellular domains
• Alpha1 and beta 1 - peptide binding cleft
• Alpha 2 and beta 2 - invariant; bind CD4 coreceptor
  
  • ***So CD4+ T cells can only respond to Class II MHC

Question 3

4 Steps of Dendritic Cell Antigen Presentation

Answer 3

• 1- capture antigen (phagocytosis, macropinocytosis, Fc receptor mediated uptake, immune complex uptake or receptor-mediated endocytosis)
• 2- TLR signaling and cytokines —> dendritic cell activation
  
  • **Develop CCR7 chemokine receptors - help DCs exit epithelium and head to lymph
• 3- migration to afferent lymphatic vessel; DCs mature while they migrate (inc synthesis and stability of MHC molecules and co-stimulators)
• 4- Concentrate in lymph nodes until T cell circulates through

Question 4

5 Features of MHC Peptide Binding

Answer 4

-Must be peptide w/in cells (produced by infected cell or ingested)

• Only MHC molecules that have assembled their chains AND bound peptide are stable enough to make it to surface; otherwise they are degraded inside cell
  (Last days- ensure that APC encounters T cell in that time)
• MHC molecules cannot distinguish self from non-self but T cells that respond to self are destroyed during maturation anyway
• Many diff peptides can bind to single MHC molecule (common peptide binding motifs)
• Ea MHC can only bind 1 peptide at a time BUT there can be must MHC molecules per cell (ea can have diff peptide but those peptides would all have same peptide binding motif)

Question 5

MHC Class I Site and Mechanism of Peptide Loading

Answer 5

• proteins that have been broken down via ubiquitin-proteosome system are in cytoplasm meet up w/ MHC molecules made in ER and are loaded there
• TAP transports these peptides from cytoplasm to ER

Question 6

MHC Class II Site and Mechanism of Peptide Loading

Answer 6

• invariant chain protein occupies peptide binding cleft while in ER
• Travel to vesicles and then DM exchanges CLIP for peptide in late vesicles

Question 7

Cross Presentation

Answer 7

• Some dendritic cells can present ingested antigens on MHC Class I molecules to CD8+ T cells (exception to rule)
• Dendritic cells ingest infected/dying cells or cell fragments —> proteasome degradation —> MHC class I —> cytotoxic T cells can now kill infected host cells or tumor cells

Question 8

Why does Class I v Class II make physiological sense?

Answer 8

Class I present peptides from intracellular microbe - so induce CD8+ T cells to destroy other infected cells

v.

Class II present peptides from ingested extracellular microbe - so induce CD4+ cells which activate B cells for extracellular antibody killing of microbe

Question 9

Lengths of MHC I and MHC II Peptides

Answer 9

Class I - 8 to 10 AAs

Class II - 12 to 20 AAs