23 - MHC

Question 1

what are MHC molecules?

Answer 1

cell surface glycoproteins

highly polymorphic

Question 2

what does the MHC do?

Answer 2

enables T cells recognition of Ag on cell surfaces

MHC I - CD8+
MHC II - CD4+

encoded by HLA genes

Question 3

what are HLA?

Answer 3

human leucocyte antigens

Question 4

what are the 2 types of MHC?

Answer 4

class I 
class II

• on different cell types
• bind antigens from different sources
• inherit 1 set from each parent

Question 5

what HLA are MHC I?

Answer 5

HLA-A
HLA-B
HLA-C

Question 6

what HLA are MHC II?

Answer 6

HLA-DP
HLA-DQ
HLA-DR

Question 7

where is the HLA locus found?

Answer 7

on chromosome 6

Question 8

MHC I structure

Answer 8

• heterodimer
• 3 alpha domains: a1,2,3
• 1 beta domain: b2 microglobulin
• binds 8-10 AA
• alpha1&2 domains form peptide binding region
• alpha3 is transmembrane domain
• beta2 microglobulin is not with the HLA complex
• polygenic - can bind lots of different antigens

Question 9

MHC II structure

Answer 9

• 2 transmembrane domains: alpha2 and beta2
• alpha1 and beta1 form peptide binding region
• binds 13-24 AA
• beta chains different to the beta microglobulin in MHC I

Question 10

where are MHC I expressed?

Answer 10

by most nucleated cells

Question 11

where are MHC II expressed?

Answer 11

only on specialised immune cells - APCs

Question 12

what do MHC I bind to?

Answer 12

CD8+ cytotoxic cells

Question 13

what do MHC II bind to?

Answer 13

CD4+ T helper cells

Question 14

peptide binding grooves of MHC I and II

Answer 14

MHC I is much smaller and doesn’t open as wide so doesn’t allow large peptides to bind

APCs are the only cells that can express both classes

Question 15

what are endogenous antigens?

Answer 15

proteins made in the cytoplasm

presented by MHC I

Question 16

what are exogenous antigens?

Answer 16

proteins made outside cell or in vesicles

presented by MHC II

Question 17

endogenous peptide presentation by MHC I

Answer 17

1) antigen synthesised in cytoplasm
2) protein cleaved to peptides by proteasome
3) peptides transported to ER by TAP
4) peptides bind to MHC I molecules
5) MHC-peptide complex transported to cell surface

Question 18

exogenous peptide presentation by MHC II

Answer 18

1) MHC II molecules in ER have invariant chain
2) MHC II moves from ER to vesicles - invariant chain broken down
3) antigen engulfed by APC
4) protein cleaved to peptides by proteases
5) vesicles with peptides fuse with vesicles with MHC II in
6) MHC II binds peptide fragments
7) MHC-peptide complex transported to cell surface

Question 19

how does the TCR signal?

Answer 19

activation of CD3 complex needed to activate signalling cascade

ITAMs are vital in sending signal cascade to nucleus to activate transcription of cytokines

residues phosphorylated when something binds which activates cascade

Question 20

what are ITAMs?

Answer 20

immune receptor tyrosine-base activation motifs

Question 21

how is MHC recognition by T cells stabilised?

Answer 21

by the co-receptors CD8+ and CD4+

Question 22

how many peptides can each MHC bind?

Answer 22

a single one at a time

can potentially bind different peptides though

Question 23

what is the sniff test?

Answer 23

if someone has a different MHC molecule to you, you are more likely to be attracted to them

it is also known to be heightened during ovulation

contraception can affect this