module 04 section 02 (antigen processing/presentation)

Question 1

what does antigen processing involve?

Answer 1

protein degradation and formation of the peptide:MHC complex

Question 2

endogenous antigens are processed through which pathway?

Answer 2

cytosolic

Question 3

exogenous antigens are processed through which pathway?

Answer 3

endocytic

Question 4

the cytosolic pathway results in the formation of which class of MHC:peptide complex?

Answer 4

MHC class I

Question 5

the endocytic pathway results in the formation of which class of MHC:peptide complex?

Answer 5

MHC class II

Question 6

what does antigen presentation involve?

Answer 6

the transport of peptide:MHC complexes to the cell membrane of the APCs where they’re displayed to T-cells

Question 7

peptide:MHC class I complex is presented by what cells?

Answer 7

all nucleated cells

Question 8

peptide:MHC class I complex is recognized by what cells?

Answer 8

CD8+ cytotoxic T-cells

Question 9

peptide:MHC class II complex is presented by what cells?

Answer 9

professional APCs

Question 10

peptide:MHC class II complex is recognized by what cells?

Answer 10

CD4+ helper T-cells

Question 11

“endogenous antigens” refers to the fact that the antigen originates where?

Answer 11

inside the cell (i.e. can be self or foreign proteins)

Question 12

foreign endogenous antigens can include: (2)

Answer 12

viruses, intracellular bacteria from infected host cells

Question 13

what are cytosolic proteins degraded by?

Answer 13

a large multicatalytic protease complex (proteasome) encoded by the LMP genes

Question 14

describe the degradation of cytosolic proteins

Answer 14

the proteasome generates peptide fragments in the cytosol, which are then transported to the ER, where they bind to MHC class I molecules

Question 15

what does the cytosolic antigen processing pathway lead to? in how many steps?

Answer 15

• the expression of a peptide:MHC class I complex on the cell surface
• 5

Question 16

what is step 1 of the cytosolic pathway?

Answer 16

(start in the lumen of the ER)

• newly synthesized MHC class I α chain rapidly binds to molecular chaperone calnexin
• this maintains a partially folded state of the α chain in the ER
• β2 microglobulin binds to the α3 chain

Question 17

what is step 2 of the cytosolic pathway?

Answer 17

• MHC class I α:β2m complex is released from calnexin and binds to calreticulin and tapasin
• tapasin functions to bring the TAP transporter to the MHC complex (to form peptide loading complex)

Question 18

what is a TAP transporter?

Answer 18

TAP1 and TAP2:
-these are ATP-binding cassette proteins involved in transporting short peptides from the cytosol into the lumen of the ER, where they associate with MHC class I molecules

Question 19

what is step 3 of the cytosolic pathway?

Answer 19

• peptide fragments from proteasome degredation in the cytosol are transported into the ER via the TAP transporter
• calreticulum bound to the MHC molecule, makes the binding groove accessible for peptide binding as it partially unfolds the molecule

Question 20

mutations in the TAP1 or TAP2 genes results in what?

Answer 20

prevents antigen presentation by MHC class I molecules bc the peptide cannot be transported into the ER

Question 21

what is the result of the lack of antigen presentation via MHC class I

Answer 21

the inability to activate CD8+ cytotoxic T-cells (likely that they’re more susceptible to infection)

Question 22

what is step 4 of the cytosolic pathway?

Answer 22

• once the peptide:MHC class I complex is formed, it dissociates from the calreticulin, tapsin, and TAP
• the complex is exported from the ER to the golgi apparatus via vesicle transport

Question 23

what is step 5 of the cytosolic pathway?

Answer 23

• the peptide:MHC class I complex is transported to the cell surface
• here these complexes can be recognized by T-cell receptors on cytotoxic T-cells

Question 24

what is “peptide editing”?

Answer 24

when a peptide binds to the MHC complex during the cytosolic pathway, but is unstable, so the complex releases it

Question 25

"exogenous antigen" refers to the fact that the antigen originates where?

Answer 25

from oustide the cell

Question 26

exogenous antigens can include: (3)

Answer 26

extracellular bacteria, toxins, proteins

Question 27

how can exogenous antigens be internalized? (3)

Answer 27

by professional APCs, receptor-mediated endocytosis, or both

Question 28

what are endocytic proteins degraded by?

Answer 28

endosomes - acidified vesciles

Question 29

what does the endocytic pathway lead to? in how many steps?

Answer 29

- the expression of a peptide:MHC class II complex on the cell surface - 5

Question 30

what is step 1 of the endocytic pathway?

Answer 30

partially folded MHC class II molecule (which assembles in the ER) is bound by the invariant chain in the ER

Question 31

what is the function of the invariant chain?

Answer 31

blocks endogenous peptides from binding to MHC class I in ER

Question 32

what is step 2 of the endocytic pathway?

Answer 32

- the invariant chain facilitates export of MHC class II molecules from the ER through the golgi apparatus - at this point it will leave the golgi in an endosome

Question 33

what is step 3 of the endocytic pathway?

Answer 33

- internalized antigens within endocytic compartments fuse with the endosome containing MHC class II molecules - the invariant chain is digested by proteolytic enzymes within the endosome, leaving behind a short fragment called CLIP, that remains bound to MHC class II molecules

Question 34

what is step 4 of the endocytic pathway?

Answer 34

- HLA-DM removes CLIP, making the binding cleft of the MHC class II molecule accessible - also catalyzes the binding of pathogenic peptides to the MHC class II molecule

Question 35

what is step 5 of the endocytic pathway?

Answer 35

- the peptide:MHC class II complex is transported to the cell surface - here these complexes can be recognized by T-cell receptors on helper T-cells

Question 36

the cytosolic pathway is involved in ___ immunity?

Answer 36

cell-mediated

Question 37

the endocytic pathwat is involved in ___ immunity?

Answer 37

humoral