Lecture 10

Question 1

Cytosolic pathogens are found where?

Answer 1

Peptides bind to: MHC I
Degraded in: Cytosol
Presented to: Effector CD8 T Cells
Effect on presenting cell: Cell death

Question 2

Cross-presentation of exogenous antigens are found where?

Answer 2

Peptides bind to: MHC I
Degraded in: Cytosol
Presented to: Naive CD8 T Cells
Effect on presenting cell: dendritic cell activates CD8 T cell

Question 3

Intravesicular pathogens are found where?

Answer 3

Peptides bind to: MHC II
Degraded in: endocytic vesicles
Presented to: Effector CD4 T cells
Effect on presenting cell: Activation to kill bacteria/parasites

Question 4

Extracellular pathogens and toxins pathogens are found where?

Answer 4

Peptides bind to: MHC II
Degraded in: endocytic vesicles
Presented to: Effector CD4 T cells
Effect on presenting cell: Activation of T cells to secrete Ig to eliminate extracellular bacteria/toxins

Question 5

Human MHC class I istoype characteristics

Answer 5

1. HLA A,B,C bind peptides that are 8/9 amino acids in length
2. polymorphic alpha chain associated with monomorphic b2m
3. class I molecule must have b2m in order to be expressed at the cell surface/bind peptides
4. samples of proteasome are at cell surface
5. MHC class I molecules are a window to inside the cell–>allow immune system to monitor events in cytoplasm and nucleus

Question 6

How are proteins targeted for degradation are generated from?

Answer 6

defective ribosomal products (DRips)–>proteins w/ error
-Ubiquitin tags defective protein

Question 7

What is immunoproteosome

Answer 7

after IFN stimulation certain units are replaced and favor generation of peptides that anchor better in MHC I molecules

Question 8

How are peptides produced in cytosol from the proteasome transported into the endoplasmic reticulum? (MHC I)

Answer 8

Peptides made from proteasome are transported to lumen by TAP

Question 9

What is TAP?

Answer 9

Transporter associated w/ antigen processing
-delivers cytosolic peptides into the ER where they bind to MHC I

Question 10

How are MHC I molecules assembled?

Question 11

Explain the MHC I presentation pathway

Answer 11

1.Partially folded MHC I alpha chains bind to calnexin until B2 binds
2. MHC I alpha:B2m complex is released from calnexin–>binds to a complex of chaperone proteins and binds to TAP
3. Cytosolic proteins are degraded to peptide fragments by the proteasome
4. TAP delivers peptide to MHC I, folding is completed

Question 12

What happens if someone is deficient in TAP?

Answer 12

-very few CD8T cells
-NO MHC class I on surface of their cells

Question 13

Human MHC II isotype characteristics

Answer 13

1. bind to 13-18 amino acids and present to CD4 T cells
2. 2 membrane bound glycoproteins
3. Alpha chain and beta chain are BOTH POLYMORPHIC
4. Expressed on antigen presenting cells (B cells, macrophages, and dendritic cells DC)
5. Allow the sampling of extracellular pathogens

Question 14

What types of cells express MHC II?

Answer 14

Antigen Presenting Cells

Question 15

Pathway of MHC II antigen presentation?

Answer 15

1.Endocytosis of pathogen
2. Degradation of pathogen in
lysosome/endosome
3. Synthesis and transport of MHC-II to
endosome
○ With the invariant chain (which
includes CLIP)
○ Invariant Chain is degraded in the
endosome leaving CLIP behind
4. Peptide is loaded onto MHC-II
○ CLIP is removed by HLA-DM with
peptides are present
5. MHC-II with antigen is transported to the
cell surface

Question 16

What does Ii (invariant chain) and CLIP (class II associated li peptide) ensure?

Answer 16

MHC II molecules will be available for binding antigen derived peptides in endosome

Question 17

What is autophagy?

Answer 17

cytosolic proteins or organelles are delivered to lysosomes for degradation

Question 18

What is bare lymphocyte syndrome, and how do you expect the Ig levels to be in these patients?

Answer 18

a congenital deficiency in MHC II expression–>deficiency in CIITA (TF that induces MHC II expression)
-Only IgM will be expressed, no isotype switching

Question 19

Which MHC has a polymorphic alpha chain and monomorphic B2m

Answer 19

MHC I

Question 20

Explain MHC I presentation

Answer 20

1. Intracellular proteins w/ errors, defective ribosomal products (DRiPs) are brought
2. Error proteins are tagged w/ ubiquitin
3. Tagged proteins are degraded by proteasome
4. Peptides made from proteasome are delivered into lumen of Endoplasmic Reticulum by TAP
5. MHC I molecules get made in ER
6. MHC I is displayed on surface of cell where it will be recognized/bind to CD8 + T cells

Question 21

What are chaparones?

Answer 21

Facilitate the folding of MHC I before presenting them to cell surface

Question 22

Is the alpha and beta chain in MHC II polymorphic or monomorphic

Answer 22

polymorphic

Question 23

Which MHC is found in every cell?

Answer 23

MHC I

Question 24

Which MHC is found only in antigen presenting cells such as B cells, Macrophages, and Dendritic cells?

Answer 24

MHC II

Question 25

Which MHC allows for the sampling of extracellular pathogens

Answer 25

MHC II

Question 26

Explain MHC II presentation

Answer 26

1. APCs bring extracellular proteins into cell
2. Proteins are broken down in ENDOSOME
3. MHC II molecules are made in ER
   4.MHC II and invariant chain (li) are transported to vesicle
4. Invariant chain forms a complex w/ MHC II that block peptide binding
5. Invariant chain is cleaved, leaving CLIP behind still blocking binding
6. CLIP gets removed and peptides can bind
7. MHC II complex is made and brought to surface
8. CD4 T cells will recognize

Question 27

What specialized mechanism do dendritic cells have?

Answer 27

Cross presentation
-can shuttle peptides taken up by endocytosis/phagocytosis into the MHC I pathway

Question 28

Why is the invariant chain and CLIP significant for MHC II?

Answer 28

The Invariant Chain is REQUIRED to transport MHC-II to the endosome.
And the CLIP domain prevents early loading of peptides (otherwise MHC-II would
preferentially be pre-loaded with self-antigens!)