MHC presentation

Question 1

which pathway do cytosolic proteins take?

Answer 1

MHC class I (unless they are cross presented)

Question 2

which pathway do extracellular proteins take?

Answer 2

MHC class II

Question 3

MHC class I presentation pathway

Answer 3

cytosolic protein broken into peptides by proteasome
peptides cross endoplasmic reticulum through Tap1 + Tap 2 = pore
inserted into binding grove of MHC I then transported to surface

Question 4

MHC II presentation pathway

Answer 4

extracellular protein is taken in an endosome, which matures
cathepsins break down proteins into peptides
invariant chain in MHC class II is snipped off, ER releases MHC II in endosome which fuses with extracellular protein endosome
transported to surface

Question 5

how are invariant chains keeping MHC in ER

Answer 5

Ii has a zipper region that promotes trimerization
has CLIP region binds to binding site
also has a ‘molecular code’ in the cytoplasmic domain that ‘tags’ MHC II-Ii for transport to the endosome

Question 6

how are invariant chains removed

Answer 6

proteasome cleaves zipper region, generating lip-10
Cathepsin S cleaves li-p10 -> alpha beta CLIP
chaperone HLA-DM releases this