MHC Complexes

Question 1

Give a brief description of the MHC I molecules

Answer 1

Member of the Ig superfamily
Three external domains, one transmembrane domain (alpha) beta microglobulin protein.
Cytoplasmic anchor
Alpha 1 and 2 domains form cleft region that binds 8-10 AA peptide fragment from Ag (Cleft is made by two sandwiching alpha helixes and a beta sheet bottom.

Question 2

Where does MHC I exhibit polymorphism?

Answer 2

Peptide binding region.

Question 3

Describe the peptide binding region of the MHC I.

Answer 3

Binding betweel alpha1/2, closed at both ends limits AA to 8-10. Some AAs anchor peptide others interact with TcR

Question 4

Define MHC promiscuity.

Answer 4

Can bind to numerous different peptides.

Question 5

The MHC is aka _____
Where is this found in our genetics?
The MHC locus encodes for which classes of molecules?

Answer 5

Human leukocyte Ag complex - HLA
Chromosome 6
Class I, II, and III

Question 6

The MHC complex is the more _____ region in the entire genome.

Answer 6

Polymorphic

Question 7

How are MHCs inherited? What is the genetic expression of MHC?

Answer 7

In linked groups called haplotypes.

One haplotype from mom and one from dad are CODOMINANT.

Question 8

How does MHC diversity affect our immune systems?

Answer 8

Provides flexibility in responding to unexpected environmental changes now and in the future. Certain people may be able to respond better than others to the same threat.

Question 9

Which HLA is the major presenter of peptides?

Answer 9

HLA-B

Question 10

Describe the genetic diversity among ethnic groups around the world of HLAs.

Answer 10

HLA-B, the major peptide presenter, varies widely around the world based on the different threats they may encounter in those areas of the world.

Question 11

Describe the different MHC loci in different species.

How many unique classical MHC I molecules per cell?

Answer 11

Organization of MHC loci differs between species - polygenic diversity is different.
Human have 6 (2 each of Class I, II, and III)

Question 12

What does MHC I present? Why?
Where is MHC I expression found?
To whom does MHC I present?

Answer 12

Intracellular Ag peptides 
Self proteins, viral infections, abnormal cells like cancer
To check that cells are healthy.
MHC I in all nucleated cells. 
To CD8+ T cells

Question 13

Describe how MHC expression can change with the conditions?

Answer 13

Proteasome recycles defective ribosomal products. Genetic/cell regulatory cycles can drive up/down MHC expression and so can cytokines. Viruses can shut down MHC to avoid detection.

Question 14

Briefly describe HLA-G

Answer 14

Non-classical MHC I molecule.
Similar to HLA class I - does not bind TcR and interacts with inhibitory receptors.

Question 15

What is the function of HLA-G

Answer 15

It is a tolerogenic molecule with limited protein variability. It has several isoforms.
Unique molecular structure with reduced cytoplasmic tail.
It modulates the immune response.

Question 16

Where is HLA-G expression?

Answer 16

Placental tissues and tumours.

Question 17

Briefly describe the MHC II molecules

Answer 17

Member of Ig superfamily
Heterodimeric with alpha and beta chains which both pass through membrane.
Binding cleft formed by alpha/beta 1 domains
Accommodates peptides of 13-18 AAs

Question 18

Define motif

Answer 18

Common sequence in peptide Ag that binds MHC molecule

Question 19

Define anchor residues.

Answer 19

AAs anchor peptide to MHC groove

Question 20

Describe the MHC II binding cleft for peptides.

Answer 20

Open ended which allows 13-18 AA lengths

Question 21

Why are MHC polymorphisms important in terms of pathogens?

Answer 21

Pathogens will always reproduce and mutate faster than humans will so the MHC polymorphisms counteract this.
Humans must have variants of each type of MHC molecule and the population must be very varied to protect from extinction.

Question 22

How can HLA alleles influence medical treatment?

Answer 22

They can be used to deal with personalized medicine. Some HLA alleles slow or accelerate different illnesses and if they are genotyped the physician can better understand how to treat the individual.

Question 23

Contrast the differences between MHCs and T/Bcells.

Answer 23

MHC molecules do not vary within the lifetime of an individual and there is a high diversity of variants at the population level.
T/B cells receptors are inconstant flux within an individual though they are roughly the same through out populations

Question 24

Briefly discuss the MHC polymorphisms and mate choosing.

Answer 24

People are more likely to choose mates based on their MHC differences ensuring their offspring will have better immune systems.

Question 25

Briefly describe MHC II Ag processing.
Where is it expressed?
To whom does MHC II present?

Answer 25

Presents extracellular peptides (pathogens).
Usually only on APCs
CD4+ T cells

Question 26

What are HLA-DM and HLA-DO?

Answer 26

HLA-DM: regulates loading of MHC II molecules to catalyze peptide exchange.
HLA-DO: acts as substrate mimic to inhibit HLA-DM mediated catalysis of MHC peptide exchange.
— DO uses CLIP to bind to avoid other peptides being presented. DM binds to MHC when viral peptides are available and then CLIP is released and MHC goes to surface.