Lecture 10

Question 1

What is the structure of the MHC class I and class II proteins?

Answer 1

class I: one long alpha chain, beta 2 microglobulin, one transmembrane domain
- peptide binds between alpha 1 and 2 region
Class II: alpha chain and beta chain, two transmembrane domains
- peptide binds between alpha 1 and beta 1 region

Question 2

What are anchor residues?

Answer 2

amino acid side chains that interact with the MHC peptide binding cleft

Question 3

What does haplotype mean?

Answer 3

a group of alleles inherited together from one parent
- e.g. the MHC loci are usually passed onto the next generation as an intact block of DNA

Question 4

How are individual MHC proteins catalogued?

Answer 4

HLA-A*02 (allele group):101 (specific protein)

Question 5

What type of antigen is recognized by B cells?

Answer 5

unprocessed antigen (carb, lipid, proteins)

Question 6

What type of antigen in recognized by T cells?

Answer 6

processed antigen (linear peptide presented in the cleft of an MHC protein)

Question 7

Where does the TCR co-receptor bind?

Answer 7

co-receptor binds to the MHC (alpha 3 or beta 2) and is not involved in peptide binding

Question 8

What structural features of a peptide are important in promoting the binding of a peptide to a specific MHC protein?

Answer 8

• the length of the peptide
• the side chains that allow binding to MHC binding cleft

Question 9

Which part of the TCR interacts with the “bulge” of the peptide that is being presented by MHC?

Answer 9

CDR3

Question 10

What is the difference between peptide binding in MHC I and II?

Answer 10

I: short peptide chain, bulge in the middle, the binding cleft is closed at both ends
II: long peptide chain, hangs outside the groove, open at both ends, lays flat

Question 11

For either MHC class I or II, would it be expected that the side chains of the amino acids in the peptide all be interacting with the floor of the cleft (being anchor residues)?

Answer 11

no, some of the aa side chains will need to interact with TCR CDR 3 region

Question 12

What is HLA?

Answer 12

Human MHC proteins that are involved in self-recognition and defence against pathogens
CD8: HLA-A, -B, -C
CD4: P, Q, R

Question 13

How many variants of HLA can you have of MHC class I? class II?

Answer 13

I: 6
II: ?

Question 14

What would happen if no MHC could bind to a pathogenic peptide?

Answer 14

no T cell activation: no adaptive immune response

Question 15

What kind situation would result in no MHC proteins that could bind the peptide?

Answer 15

Isolated societies, inbred species

Question 16

What are the three ways peptides can be loaded onto MHC proteins?

Answer 16

MHC I: endogenous and cross-presentation (and autophagy)
MHC II: exogenous and autophagy

Question 17

Where are MHC class I peptides usually derived from?

Answer 17

cytosolic proteins (self, intracellular virus/bacteria), occasionally extracellular via cross presentation

Question 18

Where are MHC class II peptides usually derived from?

Answer 18

extracellular proteins (self, bacterial and viruses in tissues not cells)

Question 19

When does autophagy occur?

Answer 19

• damaged ribosomes/organelles or large cytosolic protein aggregates are too large to be degraded by proteasome

Question 19

When does autophagy occur?

Answer 19

• damaged ribosomes/organelles or large cytosolic protein aggregates are too large to be degraded by proteasome