Lecture # 13 Antigen Processing and Presentation - Class II

Question 1

Exception to endogenous processing

Answer 1

cross presentation allows specialized DCs to endocytose virally infect cells and present via class I to naive CD8 cells.

Question 2

How does cross presentation enable exogenous proteins to be presented by Class I?

Answer 2

1) phagosome ER 2) retrotranslocation through Sec61-ER to cytosol 3) Fusion of ER and phagosome ; important for Naive CD8 T cells

Question 3

How does interferon gamma effect the functionality of the proteosome?

Answer 3

interfereon gamma induces the immunoproteosome from the constitutive proteosome by the replacement of the beta subunit with LMP2, LMP1, MECL-1.

Question 4

What type of pathogens are taken up by Class II pathway?

Answer 4

Bacterial, parasitic, fungal;

Question 5

What cells are involved in the uptake of Class II pathogens?

Answer 5

DCs, macrophages, B Cells and other APCs; secrete cytokines

Question 6

Class II presentation pathway

Answer 6

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

Question 7

What is the endosomal protease involved with degradation of pathogens?

Answer 7

Cathepsins (Cathepsin L proteolytic cleavage) (Cathepsin S CLIP processing)

Question 8

Invariant chain

Answer 8

binds to nascent class II to fill the peptide binding groove-stabilizes

Question 9

HLA-DM

Answer 9

helps catalyze the removal of CLIP and addition of processed peptides.

Question 10

Why is invariant chain important?

Answer 10

Invariant chain prevents premature binding of peptides to Class II; binds to alpha and beta chains w/clip

Question 11

CLIP

Answer 11

Class II associated invariant chain peptide prevents other peptides from binding class II.

Question 12

What enzyme cleaves Invariant chain?

Answer 12

Cathepsin S

Question 13

What does HLA-DM do specifically?

Answer 13

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;

Question 14

Exceptions to Class II rule

Answer 14

Autophagy; virally produced proteins in the cytosol gets shuttled into the lysosomes to be loaded on Class II molecules

Question 15

• Autophagy

Answer 15

the normal process of protein turnover and can be enhanced by cellular stressors—starvation—cell must catabolize intracellular proteins to provide energy

Question 16

Micro-autophagy

Answer 16

cytosol is continually internalized into the vesicular system by lysosomal invaginations

Question 17

Macro-autophagy

Answer 17

induced by starvation, double membraned autophagosome engulfs the cytosol and fuses with lysosomes

Question 18

CMA

Answer 18

chaperone mediated autophagy uses heat shock cognate protein 70 and LAMP-2 to transport cytosolic proteins to lysosomes

Question 19

Where do peptides come from (what source) that bind to Class I?

Answer 19

Peptides come from the cytosol. Endogenous. Class I is typically viral.

Question 20

What can increase proteosome function?

Answer 20

Interferon gamma induces the immunoprotesome via PA28. LMP2, LMP7, MECL-1 replaces the beta subunit.

Question 21

What is the Function of TAP?

Answer 21

Transports peptides into the ER lumen

Question 22

List the chaperone proteins associated with Class I

Answer 22

2) ERP57* 3) Calnexin* 5) Calreticulin* *-stabilizes 4) Tapasin- binds to TAP and peptide complex.