8. Processing and Presentation of Antigen

Question 1

How do T cells recognise antigens?

Answer 1

T Cell receptor (TCR)

Question 2

How does the alpha/beta receptor of T cells recognise antigen?

Answer 2

Antigen that has been processed into peptides and presented by the MHC

Question 3

What cells is MHCI present on ?

Answer 3

All nucleated cells

Question 4

How does the MHCI stimulate cytotoxic cells to kill infected cells?

Answer 4

Fas/Fas-ligand or perforin/granzyme pathway causes infected cell apoptosis

Question 5

Describe the meaning of major and histocompatibility (MHC). What are the names of the human and mouse MHCs?

Answer 5

Histocompatibility = tissue compatibility

Major = this set of genes is most important in determining tissue compatibility

Human = HLA
Mouse = H-2

Question 6

How large are the processed peptides (presented by MHC)?

Answer 6

8-9AA

Question 7

Why is the MHC required for peptide presentation?

Answer 7

without the MHC the peptides would float away - MHC required to hold the peptide to the surface of the cell

Question 8

What is the difference between MHCI and MHCII?

Answer 8

MHCI: found on all nucleated body cells, specialised to alert cytotoxic T cells to intracellular infection

MHCII: found only on professional antigen presenting cells, activate helper T cells

Question 9

What are the different types of MHC in the human body (not just the main classes)?

Answer 9

MHCI: HLA-A, HLA-B, HLA-C
MHCII: HLA-DP, HLA-DQ, HLA-DR

Question 10

What are the different types of MHC in the mouse?

Answer 10

MHCI: H-2K, H-2D, H-2L
MHCII: I-A, I-E

Question 11

How does the MHC vary between people?

Answer 11

Two chromosome are inherited (one from each parent) with 3 main MHCI genes on each (2 x A, B, C). Each gene encodes a particular variant of HLA e.g. HLA-A74.

Everyone has different HLA variants so this is why transplants don’t work (nucleotide sequence varies)

Question 12

Which is the most common MHCI for caucasian humans?

Answer 12

HLA-A2

Question 13

What is the rough structure of the MHCI? How may the chains vary between individuals?

Answer 13

Heterodimer - alpha chain and beta chain. Alpha chains vary between individuals (polymorphic) but beta chains don’t (monomorphic)

HLA-B alpha chain is most variable, HLA-C alpha chain is least variable

Question 14

Why are MHCs all different?

Answer 14

Pathogens are mutating all the time, if we all had the same MHC then pathogen may mutate and wipe out whole of population

Question 15

Describe the molecular structure of MHC. What are the three domains?

Answer 15

Beta pleated sheet (made up of beta strands) with two alpha helices on top. Alpha helices form a groove into which the peptide may sit.

Domains: Alpha (1,2,3), transmembrane segment, cytoplasmic tail

Question 16

What does the molecular structure of MHC look like?

Answer 16

2 sausages (alpha helices) on a BBQ (beta sheets)

Question 17

Why does the size of peptides bound by MHCII/MHCI vary?

Answer 17

MHCII can bind longer peptides than MHCI as the MHCII peptide binding group is open at both ends (MHCI is closed at both ends)

Question 18

What are anchor residues? Why are they necessary?

Answer 18

Whilst MHC can bind a number of different peptides, at certain positions the AA sequence of peptide needs a particular characteristic e.g. Tyrosine can poke down into a small pocket and anchor the peptide

Question 19

What other molecule is required to get optimal binding of peptide to MHCI?

Answer 19

CD8 - recognises the non-polymorphic regions of MHCI

Question 20

If a cell is CD4+ then which class of MHC will it recognise?

Answer 20

MHCII

MHCII–>CD4 –>helper T cells
MHCI–>CD8–> cytotoxic T cells

Question 21

What is the length of peptide required for MHCI and MHCII recognition?

Answer 21

MHCI: 8-9 AA long
MHCII: ~15 AA long

Question 22

What is the role of MHCI?

Answer 22

Alerts cytotoxic T cells to fact cell is infected so immune system can kill them

Question 23

How is the endogenous (antigen in cell) antigen processed for MHCI presentation after cell infection?

Answer 23

1. Proteasome is modified to immunoproteasome (genes switched on which code for extra enzymes)
2. This causes proteasome to chop up peptide into correct 7-8AA length
3. MHC, calnexin (binds to MHCI alpha and allows correct folding) and calreticulin 57 (keeps MHCI in right shape/position to enable peptides to enter groove) are produced in the ER
4. TAP1 and TAP (antigen processing transporters) pick up peptides from cytoplasm and transport them to ER
5. Peptide is bound to MHC and complex taken to cell surface and presented to cytotoxic T cells

Question 24

What is the shape of the immunoproteosome?

Answer 24

Toilet roll shaped

Question 25

What is the MHCII presentation pathway?

Answer 25

1. Exogenous antigen phagocytosed/endocytosed by macrophage/dendritic (into vesicle)
2. Enzymes in vesicle degrade proteins into peptides with help from LAMPs
3. Invariant chain (li) and MHCII also produced
4. Invariant chain put into peptide binding group where it acts a stopper, preventing peptides binding to MHCII in ER
5. MHCII/invariant chain then taken into vesicle w/ endosomes containing peptides
6. Invariant chain is chewed off and dos degrade (leaving little bit called CLIP)
7. Do and Dm pull CLIP out and put peptides in
8. MHCII shown to T helper cells

Question 26

Does the MHCI or II use endogenous/exogenous antigen?

Answer 26

MHCI uses endogenous antigen

MHCII uses exogenous antigen

Question 27

May endogenous antigens be presented by MHCII and vice versa?

Answer 27

Yes yes YES