MHC Genetics and Disease

Question 1

What is the MHC?

Answer 1

MAJOR HISTOCOMPATIBILITY COMPLEX

Question 2

What is the HLA?

Answer 2

Human Leukocyte Antigen Complex

Question 3

Where is the MHC?

Answer 3

Located on Chromosome 6

Question 4

What does the MHC consist of?

Answer 4

Transmembrane glycoproteins

Question 5

What is the main role of the HMC?

Answer 5

Present antigens on the cell surface

Question 6

What genes code for the MHC?

Answer 6

Highly polymorphic genes

Question 7

How is the MHC inherited?

Answer 7

As haplotypes from parents.

Question 8

What does the MHC locus contain?

Answer 8

2 types of highly polymorphic genes Class I and II

Question 9

What is the difference between class i and class ii MHC?

Answer 9

Different but homologous

Different tissue distribution

Question 10

Where are the glycoproteins expressed for class 1 of MHC?

Answer 10

All nucleated cells

Question 11

What is the structure of MHC class 1?

Answer 11

MHC-encoded α-chain of 45kDa

α-chain anchored to the cell membrane

Question 12

What elements are associated with the MHC Class 1 but are not covalently bonded?

Answer 12

β2-microglobulin, 12kDa, non-MHC encoded, non-transmembrane.

Question 13

How is the shape of MHC class 1 formed?

Answer 13

Peptide antigen in a groove formed from a pair of α-helicies on a floor of anti-parallel β-strands

Question 14

Where are the glycoproteins of MHC class 2 expressed?

Answer 14

Glycoprotein expression restricted to APCs

Question 15

What is APCs?

Answer 15

Macrophages

Dendritic cells

B cells

Question 16

How heavy is the alpha chain of the class 2 MHC?

Answer 16

34kDa

Question 17

How heavy is the beta chain of the class 2 MHC?

Answer 17

29kDa

Question 18

What is the structure of MHC class 2?

Answer 18

Both α and β chains anchored to the cell membrane

Peptide antigen in a groove formed from a pair of a-helicies on a floor of anti-parallel b strands

Question 19

When was a full MHC sequence complete?

Answer 19

1999

Question 20

Where do the polymorphisms occur on MHC?

Answer 20

Binding cleft

Question 21

What is the peptide binding cleft?

Answer 21

Highly specialised grooves for antigen presentation, form
stable complexes with antigens

Question 22

What size peptides do class 1 MHC accommodate for?

Answer 22

8-10

Question 23

What size peptides do class 1 MHC accommodate for?

Answer 23

13-18

Question 24

Which if the MHC classes binding cleft has an open structure?

Answer 24

Class 2

Question 25

What does MHC bind to?

Answer 25

Antigen fragments produced by infected cells Fragments from the proteolysis of foreign material.

Question 26

How does the MHC interact with T cells?

Answer 26

MHC moves to surface to present antigen for T cell recognition.

Question 27

What happens when antigens presented on surface aren't MHC bound?

Answer 27

T cell won't recognise it

Question 28

Which T cell type does class 1 MHC interact with?

Answer 28

CD8 t cell

Question 29

Which T cell type does class 2 MHC interact with?

Answer 29

CD4 t cell

Question 30

Which MHC class deals with the endogenous pathway?

Answer 30

1

Question 31

Which MHC class deals with the exogenous pathway?

Answer 31

2

Question 32

What are the 2 laws of inheritance the MHC follows?

Answer 32

Polygeny Polymorphism

Question 33

What does it mean that the MHC is polygenic?

Answer 33

Codominance, combination of α and β for MHCII and from both parents

Question 34

What does it mean that the MHC is polymorphic?

Answer 34

Have changes to the peptide binding groove.

Question 35

Does the MHC change over time?

Answer 35

The type and variant MHC molecules do not vary in the lifetime of the individual

Question 36

What are the variations in class 1 MHC?

Answer 36

A B and C

Question 37

What are the variations in class 2 MHC?

Answer 37

DP DQ and DR, but each can be alpha and beta so 6.

Question 38

Which gene can be had more than one of?

Answer 38

DR beta

Question 39

What does it mean if when an individual is heterozygous MHC?

Answer 39

The more variety the more antigens presented.

Question 40

What about cleft polymorphisms in MHC suggest the presence of polymorphism?

Answer 40

Replacement substitutions (non-synonymous) occur at a greater rate than silent substitutions.

Question 41

What is the effect of MHC on disease susceptibility?

Answer 41

Certain MHC alleles can increase susceptibility to disease Certain MHC alleles can be protective in relation to disease

Question 42

What is the problem with studying MHC disease Loci?

Answer 42

High gene density Extreme polymorphism Strong linkage disequilibrium of MHC Which makes it hard to study individual loci.

Question 43

Which gene in the MHC was found to be associated with Ankylosing Spondylitis?

Answer 43

HLA-B*27

Question 44

What is Ankylosing Spondylosis?

Answer 44

AS is a heritable chronic disease; form of inflammatory arthritis frequently affecting the spine?

Question 45

Which gene of the MHC is associated with type 1 diabetes?

Answer 45

HLA-DR-DQ haplotype

Question 46

Why is this HLA coded gene linked to diabetes 1?

Answer 46

Due to specific amino acid at position 57 of the HLA-DQ β chain

Question 47

What kinds of drugs do MHC bind?

Answer 47

Small molecules drugs

Question 48

Why is MHC binding drugs a problem?

Answer 48

Can pose a risk and cause adverse reactions

Question 49

What is AHS?

Answer 49

ABACAVIR HYPERSENSITIVITY

Question 50

What is Abacavir?

Answer 50

Anti-retroviral used to treat HIV-1

Question 51

What percentage of patients have AHS?

Answer 51

5-8%

Question 52

How was AHS avoided?

Answer 52

The implementation of HLA-B*57:01 screening prior

Question 53

What underpins selection at the MHC?

Answer 53

1. Parasite-mediated selection and MHC evolution 2. MHC-dependent sexual selection

Question 54

What is parasite-mediated selection for a rare allele advantage ?

Answer 54

New allele, then MHC advantage allele increases selection will favour pathogenic strains that are not recognised by this allele and than this pathogen will increase in frequency until recognised by a new novel MHC allele.

Question 55

What is parasite-mediated selection for a heterozygous advantage?

Answer 55

Immune competence could be substantially enhanced by heterozygosity at MHC loci, as heterozygotes recognise a wider variety of antigens derived from multiple pathogens.

Question 56

What is sexual selection?

Answer 56

The advantage that certain individuals have over other individuals of the same sex and species, in exclusive relation to reproduction.

Question 57

What are the 2 mechanisms of sexual selection?

Answer 57

Male competition (intrasexual selection) Female choice (intersexual selection)

Question 58

What is female choice?

Answer 58

To evolve it must confer a benefit in terms of reproductive success.

Question 59

What are the 2 benefits of female choice?

Answer 59

1)Females directly improve their own RS due to choice (fecundity). 2) Genetic benefits for offspring: females improve the RS of their offspring

Question 60

What is Zahavi's handicap principle?

Answer 60

The handicap is costly therefore the individual must be of sufficient quality to afford such as costly handicap.

Question 61

Why are humans a bad example of sexual selection?

Answer 61

Too complex, with too many developed background requirements for mates along with genetics.

Question 62

What is the consequence of MHC similarity?

Answer 62

Lower successful birth rate.