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Antigen processing and presentation
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Lecture notes discussing antigens and how they process and present in the immune system
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Lecture 11 – Antigen Processingand Presentation
What is the Purpose of MHC?
Unlike B cells, T cells don’t recognise the whole antigen.
TCR’s see a complex of MHC and peptide together.
T cells can express either CD4 or CD8 on their surface.
CD4+ T cells see MHC Class II/peptides.
CD8+ T cells see MHC Class I/peptides.
This recognition can but doesn’t always lead to their activation.
MHC Class I
Surface expressed by most nucleated cells of the body-not secreted.
Called human leucocytes antigen [HLA] class I in humans.
Two proteins – alpha chain and beta 2 microglobulin.
Both proteins must be present for MHC Class I to be expressed.
Alpha 3 binds to CD8 on a T cell.
Alpha chain of MHC Class I
- 3 domains: alpha 1, alpha 2, alpha 3.
- Alpha 1 and 2 form a peptide binding groove.
- Alpha 3 is structural and interacts with beta 2m.
- Alpha 3 interacts with CD8 on a T cell.
Unlike Beta 2m, MHC Class I heavy chain is very variable.
Diversity in MHC Class I
- 6 different MHC Class I molecules are expressed by any individual at once.
- HLA-A, HLA-B and HLA-C: 2 alleles for each. Co-dominantly expressed.
- Extensive polymorphism within the population.
Peptide binding by MHC Class I
- MHC Class I Is expressed by all nucleated cells – presents normal and viral peptides to T cells
for immune activation.
- Promiscuous binder, its not like TCR or BCR, it binds to more than 1 peptide sequence.
- 8-10 amino acids closed ends.
Peptides interact with MHC at key residues, these interactions are predictable.
MHC Class I peptides can bulge whereas MHC Class II peptides cannot.
TCR and MHC do not see the same residues on the peptide. You cannot easily predict TCR
interactions as it is too random.
, MHC Class II
- 2 chains, alpha and beta. The chains come together to form a peptide-binding groove.
- Called human leucocyte antigen [HLA] class II in humans.
- It is expressed by a specialised subset of cells.
- Professional antigen-presenting cells (APC’s):
o Dendritic cells.
o Macrophages.
o B cells.
- MHC Class II has an open configuration, it binds longer peptides, up to around 24 amino
acids.
- Like MHC Class I it has promiscuous binding.
- Like MHC I it is comprised of immunoglobulin folds.
- Alpha 2 pairs with beta 2.
- The binding region for CD4 is on a CD4+ T cell.
- Like MHC, the peptide must express some key anchor residues, and is more promiscuous
than MHC Class I.
MHC Class II Peptide Flexibility
- Overhangs but is flat.
- Peptides can be at different lengths.
Diversity in MHC Class II
- Like MHC Class I, 3 alleles encode MHC Class II: DR/DP/DQ.
- Huge polymorphism in each chain.
- Each encodes an alpha and beta chain.
Human HLA Expression
For MHC Class II…
- 6 possibilities due to inheritance.
- 6 possibilities of mum/dad inherited gene combinations.
12 MHC class II molecules co-dominantly expressed.
6 MHC class I molecules are co-dominantly expressed.
How do Peptides Get to the MHC?
- Antigen processing and presentation.
- 2 different routes:
o Intracellular proteins peptides MHC I CD8+ T cells. = performed by all
nucleated cells.
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