11. MHC

Question 1

what are MHCs?

Answer 1

processed microbial proteins

Question 2

what does the display of MHC instigate?

Answer 2

cell-mediated response

Question 3

which cells can only target and present Ag from phagocytosed microbes?

Answer 3

APCs

Question 4

difference between Ag recognised between a) BCR and b)TCR

Answer 4

a) protein, lipid, NA - linear and conformational epitopes

b) MHC on APC - linear epitopes

Question 5

what is the Ag attached to in a)BCR b)TCR

Answer 5

a) variable H+L chains

b) Variable regions of alpha and beta chains

Question 6

what causes signalling in

a) BCR
b) TCR

Answer 6

a) Ig-alpha and Ig-beta

b) CD3 protein

Question 7

structure of binding site in

a) BCR
b) TCR

Answer 7

a) 3 of each CDR’s in Variable heavy and light chains

b) 3 of each CDR’s in variable alpha and variable beta chains

Question 8

describe affinity of binding in

a) BCR
b) TCR

Answer 8

a) increases after Ag binding

b) very high- due to specificity

Question 9

on rate of

a) BCR
b) TCR

Answer 9

a) fast

b) slow

Question 10

off rate of

a) BCR
b) TCR

Answer 10

a) variable

b) slow

Question 11

7 similarities between BCR and TCR

Answer 11

1. part of Ig superfamily structure
2. Have N terminals where Ag bind at V regions
3. Located on cell surface
4. Work by signalling other molecules in receptor complex
5. 3 CDR’s
6. similar receptor diversity
7. VDJ gene segment structure

Question 12

After an Ag has attached to a TCR - how is the signal transduced?

Answer 12

via ITAM tails - immuno-receptor tyrosine-based activation motifs.

Question 13

3 ways TCR diversity is achieved?

Answer 13

1. somatic recombination in germline gene pools
2. Junctional diversity
3. Transcription and RNA processing

Question 14

what 2 processes are there in Abs which dont occur in TCR - in terms of diversity?

Answer 14

1. class switching

2. Ag driven hypermutation

Question 15

which cells express MHC I?

Answer 15

nucleated cells and DC in secondary LT

Question 16

which cells express MHC II?

Answer 16

APC - dendritic, B cell, Macrophage

Question 17

what type of peptides do MHC I represent?

Answer 17

endogenous

Question 18

what type of peptides to MHC II represent?

Answer 18

exogenous- have been phagocytosed

Question 19

describe MHC I structure

Answer 19

1. 3 alpha domains - 1,2,3,
2. B2 domain - not covalently associated to alpha chain
3. a1 and a2 - polymorphic - between is peptide binding cleft
4. b2 and a3 = Ig like
5. a3 - binds to CD8

Question 20

describe MHC II structure

Answer 20

1. 2 chains - 1 alpha, 1 beta, a1 a2 b1 b2
2. a1 and b1 - polymorphic - between is peptide binding cleft
3. a2 and b2 = Ig like
4. b2 = binds CD4

Question 21

difference in peptide binding groove between MHC classes

Answer 21

I - polypeptide chain only bound at edges

II - polypeptide chain bound along the whole length of MHC

Question 22

8 steps in processing of intracellular cytoplasmic pathogens

Answer 22

1. Viral pathogen enters cytoplasm
2. viral proteins are unfolded, ubiquitanised and broken down by proteases
3. viral fragments sent to ER by TAP I and TAP II - transporting associating proteins - further trimming
4. newly sythesised MHC - stabilised by chaperone and attached to linker protein (tapasin) - allows them to be located by peptide
5. MHC forms complex with viral fragments
6. complex transported by secretory network - via vesicles
7. complex presented on cell surface
8. MHC I detected by CD8 +T cells

Question 23

8 steps in processing of intracellular vesicular pathogens

Answer 23

1. APC engulfs Ag
2. phagosome fuses with lysosome = phagolysosome
3. lytic enzymes break down ag into fragments
4. phagolysosome fuses with vesicle containing MHC II
5. Class II invariant chain peptide (CLIP) is removed from the MHC II region via HLA-DM. this molecule replaces it with the Ag fragment.
6. transported to cell membrane via secretory network
7. recognised by CD4+ T cells

Question 24

describe the specificity of MHC molecules

Answer 24

broad

Question 25

5 features of MHC complex

Answer 25

1. broad specificity
2. very slow off rate - enough time for T cells to recognise
3. can only bind/display 1 Ag at a time
4. only presented on cell surface when bound to a fragment - stable
5. only present protein/peptide Ag

Question 26

on which chromosome are the MHC genes?

Answer 26

6

Question 27

MHC I genes code for which 3 proteins?

Answer 27

HLA-A
HLA-B
HLA-C

Question 28

MHC II genes code for which 3 proteins?

Answer 28

HLA-DP
HLA-DQ
HLA-DR

Question 29

what type of protein does MHC III code for?

Answer 29

complement

Question 30

what are the main antigens recognised in transplants?

Answer 30

MHC

Question 31

describe structure of Ig domain

Answer 31

2 x anti-parallel beta pleated sheets

joined by disuphide bond