Lecture 8: Antigen Processing Flashcards
What are the 2 great domains of the cell?
- Cytoplasm & contiguous structures
- Intracellular vesicles and organelles
What do CD8 T cells recognise?
CD8 T cells recognise class I molecules that bind peptides from the cytoplasm and contiguous structures like the nucleus
What is ubiquitin?
A ubiquitous cytosolic protein that ends in cysteine, which can be covalently bound to a lysine
What is the main function of ubiquitin?
Tagging proteins for degradation by the proteasome
What is ubiquitin ligation useful for?
Protein degradation, signal transduction, cell death protection and DNA repair
- ubiquitin tagged proteins are necessary for most proteins to be protealised by the proteasome
What is the proteasome?
The major proteolytic system in the cytoplasm that makes things ordered
What does the proteasome structure consist of?
barrel shaped with 4 rings, each ring has 7 members,
2 alpha rings: gates on the outside
2 beta rings: in the middle containing 3 threonine proteases
What are the 3 different proteasome types?
Constitutive proteasome, immnoproteasome, adnd thymoproteasome
What is the immunoproteasome?
- subunits have been induced by gamma interferon (Beta1i/2i/5i)
- makes c-terminus of the peptide better for the class I molecules that the peptides are directed towards
- turned on by inflammation
How does IFNy effect the immunoproteasome?
Stimulates better antigen presentation, as it up regulates MHC I and MHC II presentation
What cells express the thymoproteasome?
Expressed in cTECs for better positive selection
What is the difference between cytoplasm and cytosol?
Cytosol has organelles, cytoplasm is without
What to cytosolic proteases do?
Trim peptides after proteasome degradation
What is TAP?
Transporter for antigen presentation is a typical ATP-binding cassette (ABC)
What are TAP1/2 composed of?
Each composed of a Tapasin-binding domain, a transmembrane (TM) peptide-binding domain, and a nucleotide binding domain (NDB)
How is the ATP site of TAPs arranged?
Each ATP binding site is split between the NDBs of TAP1 and TAP2, so both must come together to hydrolyse one ATP
- the C-terminal specificity of the TAP corresponds with the specificity of the class I molecule at pocket F
- the immunoproteasome produces peptides that fit the specificity of the class I molecule at pocket F
- there is not much specificity for the N terminus of peptides that are transported hence the N-terminus may be adjusted by amino peptidases in the ER (ERAPs)
What is pocket F?
C-terminal specificity of the TAP corresponds with the specificity of class I molecules in pocket F (where the C terminal of amino acids go)
There is no specificity for the N terminus, so has to be adjusted by ER animo peptidases (ERAPs)
What are the first steps of antigen presentation pathway in class I molecules?
- translation of class I heavy chain into the ER lumen, with co-translational N-linked glycosylation
- heavy chain binds to chaperone calnexin, with glucosidases trimming N-linked glycan
- heavy chain loses calnexin and binds ß2 micro globulin
- immature class I molecule without the peptide binds chaperone Tapasin which then binds TAP
