Midterm Part 3

Question 1

What is antigen presentation?

Answer 1

When peptides are displayed on the surface of an APC in a

way that T cells can recognize

Question 2

What is an epitope?

Answer 2

the small fragment of a protein that is recognized by a
T cell, B cell or antibody
(epitope = antigenic determinant)

Question 3

Name the three MHC I proteins and three MHC II proteins

Answer 3

MHC I: HLA-A, HLA-B, HLA-C

MHC II: HLA-DP, HLA-DQ, HLA-DR

Question 4

What are the subunits of MHC-I? Which cells express MHC-I? Where do the peptides come from? How does it load peptides?

Answer 4

• alpha chain, B2M
• all nucleated cells (including APC’s)
• cytoplasm, self, bacteria, virus
• it loads 8-12 aa’s onto a closed groove

Question 5

What are the subunits of MHC-II? Which cells express MHC-II? Where do the peptides come from? How does it load peptides?

Answer 5

• alpha chain and beta chain
• professional APC’s
• extracellular, self, bacterial, viral
• > 13 aa’s, open ended peptide binding cleft

Question 6

What are the steps of the ENDOGENOUS pathway?

Answer 6

1. Cytosolic proteins are degraded into peptides by the proteosome
2. Peptides are transported into lumen of ER by TAP
3. Peptides bind to newly synthesized MHC I in lumen of ER.
4. MHC I + peptide leaves ER, moves through Golgi apparatus
5. MHC I + peptide is then displayed on cell surface for about 24 hours before being
   internalised and replaced.

Question 7

Phagocytosis by APC’s can serve two purposes:

Answer 7

1. Direct killing

2. Antigen presentation

Question 8

What are the steps of the EXOGENOUS pathway?

Answer 8

1. Protein/pathogen is internalized by APC (receptor-mediated endocytosis or phagocytosis)
2. Endosome/phagosome fuses with lysosome, and peptides are produced by proteases
3. Newly made MHC II/invariant chain leaves the ER by vesicle and goes to the Golgi body
4. MHC II vesicle fuses with the phago/endolysosome, the invariant chain degrades into CLIP, and the antigen protein replaces the CLIP
   and the MHC II is displayed for 48 hours

Question 9

What is the function of alarm cytokines?

Answer 9

increase vascular permeability, endothelial adhesion

Question 10

Where is MHC I expressed? Where is MHC II expressed?

Answer 10

All nucleated cells, APC’s (dendritic cells, B cells, macrophages and thymic epithelial cells)

Question 11

What is cross presentation?

Answer 11

MHC class I proteins display peptides derived from exogenous proteins

Question 12

What is polymorphism and what is an example of it in your immune system?

Answer 12

• The presence of many different alleles

- the six types of HLA’s are co-expressed, so you have two of each (one from each parent)

Question 13

True or false? MHC class I and MHC class II protein present peptides to B cells and T cells.

Answer 13

False

Question 14

What is the function of CD3

Answer 14

signaling to stimulate T cell proliferation &

activation

Question 15

What is the function of paired TCRa and TCRB chains?

Answer 15

specific recognition of an epitope presented in the

peptide-binding cleft of an MHC

Question 16

What is the function of the CD4 or CD8 co-receptor

Answer 16

Strengthening the connection between the MHC/TCR complex

Question 17

Which region of the TCR dictates specificity?

Answer 17

The variable region of the alpha/beta chains

Question 18

What is included in the TCR complex?

Answer 18

1. TCR (α + β chains)
   +2. CD3 (γ, δ, ε, and ζ chains)
   +3. CD4 or CD8 co-receptor

Question 19

What are the goals of thymic T cell development?

Answer 19

• Generate TCR diversity

* Eliminate self-destructive T cells

Question 20

What is positive T cell selection?

Answer 20

only thymocytes that have a TCR capable of weakly binding to MHC proteins of thymic cortical epithelial cells (displaying self-peptides) are permitted to mature

• if it doesn’t bind: dies by neglect
• binds with high affinity: dies by apoptosis

Question 21

How are T cells tested for positive selection?

Answer 21

They are tested against Cortical thymic epithelial cells (express high levels of MHC class 
I and II)

Question 22

How are T cells tested for negative selection? What is negative selection?

Answer 22

Negative selection: To eliminate self-reactive T cells, protect against autoimmune, test self-tolerance)

The three rounds:

1. Thymic cortical epithelial cells (housekeeping genes)
2. Macrophages and DC’s (housekeeping genes)
3. Medullary thymic epithelial cells (AIRE)

Question 23

What are the three possible outcomes of negative T cell selection?

Answer 23

• TCRs bind too strongly; negative selection, apoptosis occurs
• TCRs bind “just right”; cell exits the thymus to circulation
• TCRs bind with relatively high affinity, become T regulatory cells

Question 24

Do T cell precursors (thymocytes) express a TCR?

Answer 24

T cell precursors (known as thymocytes) do not express a TCR (they’re naked)

Question 25

What is the structure of a TCR?

Answer 25

• Alpha/beta chain with V and C region
• signalling subunit CD3
• CD4 OR CD8 co-receptor

Question 26

How do Treg cells differ from T cells?

Answer 26

Treg cells express high levels of C525

Question 27

True or False: If the TCR of a thymocyte binds MHC very tightly, it will be positively selected and retained.

Answer 27

True