Lecture 7 - Antigen Processing Flashcards
Where (cell cytosol or exogenous) does antigen that is presented via MHC I come from?
Cytosol OR exogenous via the cross-presentation pathway
What kind (foreign vs. self) of antigen is usually presented on MHC I?
Self usually - fragments of old cytosolic proteins digested by proteosome.
Name three categories of foreign/diseased antigen source that might be presented on MHC I.
Viral
Neoplastic
Parasitic
Which cell types do NOT express MHC I?
Non-nucleated cells e.g RBC
CNS neurons
Where (cell cytosol or exogenous) does antigen that is presented via MHC II come from?
Exogenous only
Which MHC molecule and pathway do B cells use when they present antigen captured by membrane-bound antibodies?
MHC II - exogenous ag pathway
Which presentation pathway is used by most vaccines?
MHC II
Which protein binds the MHC I alpha chain until the beta-2 microglobulin is ready?
Calnexin
Which two proteins block the MHC I antigen-binding-site until cytosolic antigen arrives?
ERP57/ calrticulin and tapasin
Which protein imports peptides from the cytosol into the ER for MHC I loading? Does it bind any proteins to faciliate this?
TAP
Yes, binds tapasin
Give one virus which blocks peptide entry to the ER and give its mechanism
Herpes simplex -
blocks peptide binding to TAP via ICP47 protein
HCMV - blocks TAP ATPase activity via US6 protein
Bovine herpes - inhibits TAP peptide transport
Give one virus which causes retention of MHC I in the ER. How do they do this?
Adenovirus (via E19 protein) - competitive inhibition of tapasin
HCMV - Interfere with tapasin function
murine CMV
Give ones virus that degrades MHC I
HCMV, murine gamma herpes virus
Give one virus that binds MHC I at the cell surface
Murine CMV via US11 and derlin
In which species do activated T cells express MHC II?
Humans and ruminants
Where in the cell are MHC I molecules loaded? What about MHC II?
MHC I = endoplasmic reticulum
MHC II = lysosome
What structure prevents MHC II binding self-peptide?
Invariant chain (initially), then CLIP later
How many MHC II can the invariant chain bind at once?
Three
What molecule needs to bind MHC II for CLIP to leave?
HLA-DM
In which ‘direction’ does cross presentation occur?
Exogenous ag > MHC I
Don’t get endogenous ag > MHC II
How does exogenous antigen get into the ER?
Exported out of phagosome by Sec61. From cytosol, moved into ER by TAP.
Why is cross presentation important?
Activation of CD8 T cells specific for virus that doesnt infect dendritic cells or other APCs.
