MHC

Question 1

How do you describe genetically similar organisms or tissues?

Answer 1

Syngeneic

Question 2

How do you describe genetically dissimilar organisms or tissues of the same species?

Answer 2

Allogeneic

Question 3

What genes encode antigens?

Answer 3

HLA genes in humans
H2 genes in mice

Question 4

What is the function of the major histocompatibility complexes?

Answer 4

Essential for recognition of peptide antigens by T cells

Question 5

Which chromosome are human HLA genes located on?

Answer 5

Chromosome 6

Question 6

Which chromosome are mice H-2 genes located on?

Answer 6

Chromosome 17

Question 7

What genes are found in Class III region?

Answer 7

Genes encoding immune regulatory molecules = tumour necrosis factor, C3-5 complement proteins and heat shock proteins

Question 8

How are MHC alleles expressed?

Answer 8

Codominantly = both are expressed so you get a combined phenotype

Question 9

Define locus

Answer 9

Physical position on chromosomes where genes are found

Question 10

Describe allele

Answer 10

Variant of particular polymorphic gene in the population

Question 11

Define polymorphism

Answer 11

Variation of a specific DNA sequence

Question 12

Define haplotype

Answer 12

Subset of all alleles on a specific chromosome in the population

Question 13

Define diplotype

Answer 13

Subset of all genotypes on homologous chromosome pairs in the population

Question 14

What determines the degree of polymorphism/?

Answer 14

Determined by the number of alleles at each locus

Question 15

Are MHC genes polymorphic?

Answer 15

Highly

Question 16

What does an individual carry up to 6 of?

Answer 16

Individual carries up to 6 different Class I MHCs

Question 17

What is the structure of Class I MHC?

Answer 17

Hetrotrimeric complex = heavy chain, light chain and peptide antigen

Question 18

What is the Class I heavy chain made of?

Answer 18

3 alpha glycoprotein domains = transmembrane protein

Question 19

Which domains make up the Class I peptide binding groove?

Answer 19

Alpha 1 & 2

Question 20

What makes up the light chain?

Answer 20

Beta 2 microglobulin

Question 21

Where are the genes that encode the b2m of Class I MHC?

Answer 21

The genes are outside the MHC region

Question 22

How many amino acids long can Class I peptide groove bind?

Answer 22

8-10 amino acids

Question 23

Why do Class I MHC bind smaller peptide antigens?

Answer 23

Their MHC groove has closed ends and the antigen has to fit wholly into the bowl

Question 24

Can Class I MHC bind a variety of similar peptides?

Answer 24

Yes, because only specific parts of the antigen are registered

Ony 2-3 amino acids anchor the peptide to the MHC

Question 25

What activates MHC molecules?

Answer 25

Binding of antigen

Question 26

What is the structure of Class II MHC?

Answer 26

Heterotrimeric complex = alpha-chain, beta-chain and peptide antigen

Question 27

Which domains make up the Class II peptide binding groove?

Answer 27

Alpha 1 & Beta 1

Question 28

Describe Class II MHC binding groove?

Answer 28

Open ended

Question 29

How many amino acids long can Class II MHC bind?

Answer 29

13-17

Question 30

Which cells express Class I MHC?

Answer 30

All nucleated cells (not RBCs)

Question 31

Which cell express Class II MHC?

Answer 31

Only expressed in APC

Question 32

Name APCs

Answer 32

T cells B cells Dendritic cells Macrophages Thymic epithelial cells

Question 33

When can non-APCs express Class II MHCs?

Answer 33

Inflammatory conditions

Question 34

What role does TCR recognizing MHC-peptide complex play?

Answer 34

T cell development and activation

Question 35

Why can one person's T cells not recognize antigens presented on another person's MHC?

Answer 35

Because people have different MHC types

Question 36

Where are Class I MHC found?

Answer 36

Mainly in the cytosol of any cell and are presented to cytotoxic T cells leading to cell death

Question 37

Where are Class II MHC found?

Answer 37

In endocytic vesicles of APCs and are presented to helper T cells

Question 38

What effects can B cell activation cause?

Answer 38

Secretion of antibodies to eliminate extracellular bacteria/toxins

Question 39

What effect can macrophage activation cause?

Answer 39

Killing of intra vesicular bacteria and parasites

Question 40

Where are proteosomes found?

Answer 40

Cytosol

Question 41

Which part of proteosomes recognize ubiquitin?

Answer 41

19S regulatory cap

Question 42

Where are TAP1/2 proteins found?

Answer 42

ER membrane

Question 43

What is the function of TAP1/2 proteins?

Answer 43

Transport viral peptides from cytosol onto Class I MHC molecules in the ER

Question 44

Where does ATP bind on TAP1/2 proteins?

Answer 44

ABC domain = ATP-binding cassette

Question 45

How are Class I MHC assembled?

Answer 45

Partly folded alpha chain binds to calnexin until beta 2 microglobulin binds Released from calnexin and binds chaperone proteins = calreticulin and Erp57

Question 46

How do Class I MHC present antigens?

Answer 46

Class I MHC bind to TAP via tapasin Cytosolic proteins are degraded to peptide fragments by proteasome TAP delivers peptides to Class I MHC = completing its folding Fully loaded Class I MHC is released from TAP complex and exported

Question 47

What does the partly folded alpha chain of Class I MHC bind?

Answer 47

Calnexin

Question 48

What are the two charperone proteins Class II MHC binds?

Answer 48

Calreticulin and Erp57

Question 49

What allows Class I MHC to bind to TAP?

Answer 49

Tapasin

Question 50

How are antigens bound to Class II MHC?

Answer 50

Antigens taken up in intracellular vesicle Early endosomes = endosomal proteases are inactive (neutral pH) Acidification of vesicles activates proteases = degrade antigen into peptide fragments Vesicle with peptides fuse with vesicles containing Class II MHC molecules

Question 51

How does Class II MHC antigen presentation occur?

Answer 51

Invariant chain forms a complex Class II molecules = blocks binding of peptides and misfolded proteins Invariant chain is cleaved in an acidified endosome = leaving short peptide fragment (CLIP) Endocytosed antigens are degraded to peptides in endosomes = CLIP still blocks binding HLA-DM binds to Class II MHC = releasing CLIP Class II MHC then travels to cell surface