Chapter 6: Antigen presentation to T lymphocytes Flashcards
What two things does Antigen presentation do? What do dendritic cells do?
- Arm effector T cells and trigger their effector function
Dendritic cells activate CD8 and CD4 T cells (bridge bt innate and adaptive)
What do INF-γ and IL-21 do?
- Generate alpha T-cell receptor
How are antigens processed? Where can the antigen be acquired?
- Intracellular degredation of foreign protein into a peptide that can bind to MHC molecules for presentation to T cells
- Cytosol or vesicular system (ER, golgi, lysosome, endosome)
What happens when MHC I has an antigen attached?(cytosolic)
- CD8 cytotoxic T cell will kill it (direct presentation)
What happens when MHC II has an antigen attached? (endosome of phago or macro)
- MHC II presents to a CD4 (NOT helper) T cell to activate cytokine production activating the macrophage
What happens when an extracellular pathogen attaches to a cell surface receptor and enters via endocytosis?
- Antigens are presented by MHC II to CD4 Helper T cells which stimulate B cells to make antibodies
Outline the steps in cytosolic and vesicular processing of MHCs.
Cytosolic:
- Virus enters proteosome and is broken down into peptides where it enters ER and attached to MHC I which can be sent to cell surface to present to CD8
Vesicular:
- antigen is uptaken by endosome which breaks down peptide and MHC II from ER attaches to peptide to present on surface to CD4
How are peptide fragments formed?
- Proteosome complex combines in cyotosol
- Protein is ubiquinated and recognized by the proteosome
- Different proteosomes form different peptide fragments
- Protein is degraded in catalytic core and released into cytosol
What happens to the peptide fragments released into the cytosol? WHat do interferons do?
- Peptides transported by TAP into ER where it is further processed before binding to MHC I
- Expression enhanced by interferons
- Transport 8-16 amino acids in length
What is Calnexin? How can peptides bind if they’re low affinity?
- Chaperone protein plays a central role in the assembly of immunological proteins
- Associates with TCR, MHC II, antibodies
- Peptides with low binding affinity are replaced with high binding affinity (peptide editing)
How are MHC II complexes generated?
- Made in acidified endocytic vesicles from proteins (obtained by phago,autophagy,endo)
- Peptide fragments generated by various proteases that are active at low pH
What does the invariant chain do? What happens when it binds to MHC II? What is left after the degredation
- Directs the MHC II molecule to acidified vesicle
- Invariant chain prevents the binding of peptides and unfolded proteins to MHC II
- Once invariant chain is fully assembled, MHC II is released from Calnexin and transported out of ER
- After degradation, CLIP remains
How are HLA-DM, HLA-DO related to CLIP and MHC II?
- HLA-DM,DO regulate the exchange of CLIP for other peptides
- HLA-DM binding to MHC II releases CLIP
- HLA-DO is negative regulator that binds to HLA-DM until endocytic compartment is acidified
Can autophagy deliver cytosolic antigens to MHC II?
- Autophagy can deliver cytosolic antigens for presentation by MHC II molecules
How is a dendritic cell used? What is cross-presentation?
- Dendritic cells use cross-presentation to present exogenous proteins on MHC I molecule to prime CD8 T cell
- Cross presentation is a process in which extracel. proteins taken up by dendritic cells which can give rise to peptides presented by MHC I molecules
- T cell activation (cross priming)
What is a superantigen? What does it cause?
- Illicits T cell response. Bind independently to MHC II and TCR
- They’re not processed
- Cause a massive production and release of cytokines from CD4 cells
- systematic cytotoxicity and supress adaptive immune
