L7

Question 1

What does the T cell receptor recognize in its binding? Why is that important?

Answer 1

Need BOTH the correct MHC class AND peptide with epitope for TCR

Question 2

How do MHC 1 and 2 differ in their basic protein structure?

Answer 2

MHC1
- alpha 1, alpha 2, alpha 3, beta2 microglobulin
- binds short peptides - closed into groove by internal H or ionic bonds
MHC2
- alpha 1 + alpha 2 & beta 1 + beta 2
- alpha/beta2 parts = transmembrane
- longer peptides, ends can stick out

Question 3

What proteins form the groove for MHC1? Where is the variability found?

Answer 3

Alpha 1 & 2 = groove where peptide lies
- Variability in alpha helices or beta pleated sheet that makes the floor of the groove
Alpha 3 = constant region where CD8 binds

Question 4

What proteins form the groove for MHC2? Where is the variability found?

Answer 4

Alpha 1 & beta 1
Beta 2 = where CD4 attaches
Variability = BETA 1

Question 5

If you were immunized with a live virus that could replicate within your cells, which MHC would most likely present the viral peptides?

Answer 5

MHC1

Question 6

B cells would most likely express what types of MHC on their cell surface? What about skin cells?

Answer 6

B cells - MHC 2 (b/c APC)

Skin cell - MHC 1

Question 7

What does beta2 microglobulin bind? What does does it interact with?

Answer 7

MHC 1 - alpha 3

Question 8

What type of peptides bind MHC1?

Answer 8

SMALLER

Right anchoring resides at positions 2, 5, 8/9

Question 9

How are peptides processed for MHC1 presentation?

Answer 9

Breakdown in proteosome
Peptide products transported by TAP –> ER
Tapasin holds MHC next to TAP so the peptide can be loaded
MHC+peptide together –> golgi –> vesicles –> membrane

Question 10

What happens if MHC1 presenting cells are treated with IFN gamma?

Answer 10

Proteosomes become better at making peptides that will fit into MHC molecules
Boosting likelihood of getting peptides that will work in the groove

Question 11

Explain peptide processing for MHC2.

Answer 11

Uptake of extracell via phagocytosis
Lysosome into peptides
Invariant chain sticks into middle of MHC2 for transport stability –> temporary clip inside groove
Vesicles with peptides & MHC2 fuse –> invariant chain cleaved
HLA-DM has higher affinity for temporary clip –> now any peptides in phagosome can bind the empty MHC2 groove

Question 12

Where is MHC loading in 1 vs 2?

Answer 12

1: ER
2: Vesicles moving toward membrane

Question 13

What are class 1 HLA gene products? Class 2? Class 3?

Answer 13

Class 1 = HLA A, B, C
Class 2 = HLA DQ, DP, DM & TAP, taposin
Class 3 = complement

Question 14

Are MHC 1 or 2 isotypes more polymorphic?

Answer 14

Class 1