8. Processing and Presentation of Antigen Flashcards
How do T cells recognise antigens?
T Cell receptor (TCR)
How does the alpha/beta receptor of T cells recognise antigen?
Antigen that has been processed into peptides and presented by the MHC
What cells is MHCI present on ?
All nucleated cells
How does the MHCI stimulate cytotoxic cells to kill infected cells?
Fas/Fas-ligand or perforin/granzyme pathway causes infected cell apoptosis
Describe the meaning of major and histocompatibility (MHC). What are the names of the human and mouse MHCs?
Histocompatibility = tissue compatibility
Major = this set of genes is most important in determining tissue compatibility
Human = HLA Mouse = H-2
How large are the processed peptides (presented by MHC)?
8-9AA
Why is the MHC required for peptide presentation?
without the MHC the peptides would float away - MHC required to hold the peptide to the surface of the cell
What is the difference between MHCI and MHCII?
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
What are the different types of MHC in the human body (not just the main classes)?
MHCI: HLA-A, HLA-B, HLA-C
MHCII: HLA-DP, HLA-DQ, HLA-DR
What are the different types of MHC in the mouse?
MHCI: H-2K, H-2D, H-2L
MHCII: I-A, I-E
How does the MHC vary between people?
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)
Which is the most common MHCI for caucasian humans?
HLA-A2
What is the rough structure of the MHCI? How may the chains vary between individuals?
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
Why are MHCs all different?
Pathogens are mutating all the time, if we all had the same MHC then pathogen may mutate and wipe out whole of population
Describe the molecular structure of MHC. What are the three domains?
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
What does the molecular structure of MHC look like?
2 sausages (alpha helices) on a BBQ (beta sheets)
Why does the size of peptides bound by MHCII/MHCI vary?
MHCII can bind longer peptides than MHCI as the MHCII peptide binding group is open at both ends (MHCI is closed at both ends)
What are anchor residues? Why are they necessary?
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
What other molecule is required to get optimal binding of peptide to MHCI?
CD8 - recognises the non-polymorphic regions of MHCI
If a cell is CD4+ then which class of MHC will it recognise?
MHCII
MHCII–>CD4 –>helper T cells
MHCI–>CD8–> cytotoxic T cells
What is the length of peptide required for MHCI and MHCII recognition?
MHCI: 8-9 AA long
MHCII: ~15 AA long
What is the role of MHCI?
Alerts cytotoxic T cells to fact cell is infected so immune system can kill them
How is the endogenous (antigen in cell) antigen processed for MHCI presentation after cell infection?
- Proteasome is modified to immunoproteasome (genes switched on which code for extra enzymes)
- This causes proteasome to chop up peptide into correct 7-8AA length
- 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
- TAP1 and TAP (antigen processing transporters) pick up peptides from cytoplasm and transport them to ER
- Peptide is bound to MHC and complex taken to cell surface and presented to cytotoxic T cells
What is the shape of the immunoproteosome?
Toilet roll shaped
What is the MHCII presentation pathway?
- Exogenous antigen phagocytosed/endocytosed by macrophage/dendritic (into vesicle)
- Enzymes in vesicle degrade proteins into peptides with help from LAMPs
- Invariant chain (li) and MHCII also produced
- Invariant chain put into peptide binding group where it acts a stopper, preventing peptides binding to MHCII in ER
- MHCII/invariant chain then taken into vesicle w/ endosomes containing peptides
- Invariant chain is chewed off and dos degrade (leaving little bit called CLIP)
- Do and Dm pull CLIP out and put peptides in
- MHCII shown to T helper cells
Does the MHCI or II use endogenous/exogenous antigen?
MHCI uses endogenous antigen
MHCII uses exogenous antigen
May endogenous antigens be presented by MHCII and vice versa?
Yes yes YES
