Module 7: Antigen Processing and Presentation Flashcards
What are the steps of antigen processing and presentation?
1) Introduction of exogenous proteins into vesicles OR synthesis of antigens in the cytosol
2) Proteolytic degradation
3) Binding of peptides to MHC molecules
4) Display at cell surface
Describe endogenous processing (MHC I presentation)
1) Intracellular proteins are tagged with ubiquitin
2) Ubiquitinylated proteins are targeted for degradation by proteasomes
3) Peptides are transported from the cytosol to the rough ER, transported through TAP molecules
4) Newly synthesized MHC I molecules associate with TAP and receive incoming peptides, helped by chaperones
5) Peptide-MHC I complex move out of the ER, through the golgi, to the cell surface
What are TAP molecules?
ATP-dependent channels embedded in the ER; Transporters associated with Antigen Processing
What are some chaperones that aid in MHC I-peptide assembly?
1) Calcinexin and tapasin, etc. help fold MHC I and brings it near TAP
2) ERAP1 trims peptides into a suitable size for the MHC I groove
Describe exogenous processing (MHC II presentation)
1) Exogenous proteins are taken into the cell via endocytic vesicles
2) Proteins are cleaved into peptides by enzymes that activated at acidic pH
3) MHC II molecules are produced in the ER, initially associated with invariant chain (li), and exported to the golgi
4) MHC II-containing vesicles fuse with late endosomes containing peptides
5) li is degraded, CLIP remains in the groove of MHC II
6) HLA-DM exchanges CLIP with peptide fragment
7) Complex is brought to surface
What is the function of the invariant chain (li)?
The invariant chain guides vesicles containing MHC II to late endosomes and prevents peptides from binding to the groove too early
Which cells can cross-present/cross-prime?
DCs - they capture and ingest virus-infected or tumor cells and present associated antigens to CD8+ T cells via MHC I presentation
Why is cross-presentation important?
It allows for activation of CD8+ T cells against intracellular infection when the infected/tumor cells are unable to present antigens themselves, and even if the DC itself is not infected
Why is “licensing” required for DCs to be able to cross-present?
To prevent continual redirection of self-antigens to APC pathways
How are DCs licensed for cross-presentation?
1) If they are able to present exogenous antigens to CD4+ T helper cells
2) If they receive proper cytokine signaling between APCs and helper T cells
How do T cells recognize non-protein antigens?
CD1 and MR1 (MHC I related protein) can present lipids and lipid-linked molecules
