Vocabulary and Objectives Week 7 Flashcards
PA28
binds to either end of inducible proteosome; Opens up the ends and increases rate at which peptides are released; induced by IFN-g
Proteosome
large protease complex that degrades cytosolic proteins
Constitutive Proteosome
Always on; has alpha and beta subunits
Immunoproteasome
Induced by IFN-g; LMP2, MECL-1, LMP7
TAP
binds peptides from cytosol and transports them to the ER lumen to bind to Class I MHC
ERAAP
Endoplasmic reticulum aminopeptidase associated with antigen processing; responsible for further processing of peptides so they can better fit into MHC I
Rule 1
endogenous antigens are processed and presented in the class I pathway to CD8 T cells, endogenous antigens are found inside the cell
Exception to Rule 1
cross presentation allows specialized DC to endocytose virally infected cells and present via class I to naïve CD8 cells; DC can take up pieces of virally infected cells in the endosome that then gets shuttled to the cytosolic compartment to be chopped up via the proteosome
How do proteins from phagosome get into cytosol?
Phagosome to cytosol; Retro-translocation through Sec61-Endosome to ER; Fusion of ER and phagosome
Calnexin
Binds to MHC I until B2m can bind
What three proteins bind to MHCI and stabilize it in the ER?
Calreticulin, Erp57 and calnexin
Tapasin
Binds to TAP and aids in TAP presenting peptides to MHC I
Antigen processing
refers to the generation of peptides from an intact antigen that involves modification of native protein
Antigen presentation
refers to the display of the peptide at the cell surface by MHC molecules to T cells
CLIP
Class II Invariant Chain Peptide; sits in the peptide binding cleft of MHC II; stabilizes MHC II and keeps peptides from binding
HLA-DM
acts as a peptide exchanger, facilitating the removal of CLIP and the addition of other peptides to class II MHC molecules
Autophagy
enzymatic digestion of cytoplasmic contents
Invariant Chain
Blocks premature binding of Class II MHC; promotes folding and assembly of class II MHC molecules and directs newly formed class II MHC molecules to the late endosomes and lysosomes; degraded by cathepsins
Cathepsins
proteases in endosomal compartments, for class II,
Evasins
can degrade class I or bind to TAP and inhibit peptide loading
MIIC endosomal Compartment
contains the enzymes that degrade protein antigens, class II MHC molecules, and two molecules involved in peptide loading of class II MHC molecules, the invariant chain and HLA-DM
Where is the Class II MHC molecule generated?
Class II MHC molecules are synthesized in the ER and transported to endosomes with an associated protein, the invariant chain, which occupies the peptide-binding clefts of the newly synthesized class II MHC molecules
