Flashcards in Lecture # 13 Antigen Processing and Presentation - Class II Deck (22):
Exception to endogenous processing
cross presentation allows specialized DCs to endocytose virally infect cells and present via class I to naive CD8 cells.
How does cross presentation enable exogenous proteins to be presented by Class I?
1) phagosome ER 2) retrotranslocation through Sec61-ER to cytosol 3) Fusion of ER and phagosome ; important for Naive CD8 T cells
How does interferon gamma effect the functionality of the proteosome?
interfereon gamma induces the immunoproteosome from the constitutive proteosome by the replacement of the beta subunit with LMP2, LMP1, MECL-1.
What type of pathogens are taken up by Class II pathway?
Bacterial, parasitic, fungal;
What cells are involved in the uptake of Class II pathogens?
DCs, macrophages, B Cells and other APCs; secrete cytokines
Class II presentation pathway
1) uptake of intracellular proteins 2) processing of uptaken proteins in the endosomal/lysosomal vesicles 3) Transport of MHC II molecules to endosomes 4) Association with Class II MHC molecules in vesicles 5) Expression
What is the endosomal protease involved with degradation of pathogens?
Cathepsins (Cathepsin L proteolytic cleavage) (Cathepsin S CLIP processing)
binds to nascent class II to fill the peptide binding groove-stabilizes
helps catalyze the removal of CLIP and addition of processed peptides.
Why is invariant chain important?
Invariant chain prevents premature binding of peptides to Class II; binds to alpha and beta chains w/clip
Class II associated invariant chain peptide prevents other peptides from binding class II.
What enzyme cleaves Invariant chain?
What does HLA-DM do specifically?
mediates the removal of invariant chain, also catalyzes the exchange of CLIP with processed peptides; also catalyzes the release of unstably bound peptides from class II molecule;
Exceptions to Class II rule
Autophagy; virally produced proteins in the cytosol gets shuttled into the lysosomes to be loaded on Class II molecules
the normal process of protein turnover and can be enhanced by cellular stressors—starvation—cell must catabolize intracellular proteins to provide energy
cytosol is continually internalized into the vesicular system by lysosomal invaginations
induced by starvation, double membraned autophagosome engulfs the cytosol and fuses with lysosomes
chaperone mediated autophagy uses heat shock cognate protein 70 and LAMP-2 to transport cytosolic proteins to lysosomes
Where do peptides come from (what source) that bind to Class I?
Peptides come from the cytosol. Endogenous. Class I is typically viral.
What can increase proteosome function?
Interferon gamma induces the immunoprotesome via PA28. LMP2, LMP7, MECL-1 replaces the beta subunit.
What is the Function of TAP?
Transports peptides into the ER lumen