Ingham-7: MHC II Flashcards
What does dRIPs stand for?
defective ribosomal products
How are dRIPs produced?
- improperly spliced mRNAs
- ribosomal frameshifts
Where are amino acids ubiquitylated?
epsilon amino group of Lys
Describe components of 26S proteosome
- 19S “lid”
- 20S core
Function of 19S lid (x3)
- binds ubiquitin
- unfolds proteins that are not completely folded
- recycles ubiquitin
Function of 20S core
contains proteasomes that chop up proteins
What is special about 20S core in proteasome of pAPCs?
it has a special subunits to make the immunoproteasome
What proteases are in the immunoproteasome?
LMP2, LMP7, LMP10
What cytokines upregulate the expression of subunits of the immunoproteasome?
IFN-gamma and TNF-alpha
Importance of PA28
allows increased peptide generation
What does PA28 replace in immunoproteasome?
19S
Function of TAP
- ATP-dependent transporter that transfers peptides into RER
Where are the alpha and beta-2 microglobulin chains synthesized?
RER lumen
Function of calnexin and ERPp57?
bind partially folded alpha chain (help fold it)
Components of the peptide loading complex
- TAP transporter
- Calreticulin
- Tapasin
- ERp57
Function of tapasin
links TAP to alpha chain and beta-2 microglobulin complex
Function of ERp57 (more specific)
breaks and reforms disulfide bonds to help fold alpha chain
Mutations in what genes cause bare lymphocyte symdrome type 1
TAP1 or TAP2 genes
What does MIIC stand for?
MHC Class II-containing compartment
Where are the alpha and beta chains for MHC II synthesized?
RER
Function of the invariant chain (Ii)
x3
- prevents peptides from binding to MHC II in RER
- helps fold MHC II
- directs MHC II out of ER and towards low endosomal compartments
Function of cathepsinf
- cleaves Ii in acidic vesicles
Function of CLIP
prevents peptides from binding to peptide biding groove
Significance of the MIIC late endosome
- MHC II/CLIP complex meets broken down peptides and binds them
Function of HLA-DM
binds MHC II/CLIP complex and promotes release of CLIP and binding of internalized peptide
What mutations cause bare lymphocyte syndrome type 2?
mutations in TFs that promote MHC II expression
What is cross presentation?
exogenous Ags can get into the Class I pathway