2. Antigen Presentation Flashcards
What is MHC?
- A set of molecules the immune system uses to identify self and non-self and tell the difference between them.
- Class 1 and 2
- Human Leukocyte Antigen in humans.
- Important in Adaptive and antigen specific responses.
What is the biggest immunological problem?
How does the body what is self and what is not.
How do we know adaptive immunity if evolutionarily successful?
Everything has an immune system.
How does the structure of proteins allow for specific recognition in immunity?
- They can be broken down into small chains of 13-20 amino acids.
- There are 20 different amino acids possible for each position in the chain.
- Therefore huge numbers of unique amino acid chains that can be used to identify foreign bodies.
How was the MHC’s role in antigen restricted killing proved?
- In 1973, a Nobel prize-winning paper looked at restriction in mouse MHC molecules.
- They used a chromium assay to show the point of cell death (chromium is released on death).
- Only a certain cell type was killed by the immune cells showing restricted killing of cells.
- This paper showed that MHC stimulated or delivered something to the cells to enable killing.
What made identifying MHC structure possible?
improved scientific techniques to identify crystal structures.
What does MHC do?
Present different peptides to a TCR on a naive T cell
What antigens are presented on MHC1?
- Intracellular antigens processed in the cytosol
- presented to CD8+ T cells
What antigens are presented on MHC2?
- Extracellular antigens that are endocytosed and degraded in an endosome.
- Presented to CD4+ T cells
How many peptides do APC present?
Many different peptides on many different MHC molecules
How many peptides can bind a TCR?
1 unique peptide
What educates the immune system?
The peptidome displayed in the thymus during clonal selection and central tolerance.
How does the T cell repertoire arise?
- All the T cells are produced and mature in the thymus.
- The peptidome of the individual is displayed in the thymus determines the thymocytes that survive.
- This means every immune system is different with different T cells.
When is the immune system active?
- It is always active and surveying the antigens displayed but it is not fully active when self peptides are expressed as the immune system has learnt to recognise and tolerate yourself.
- It is fully activated when a foreign antigen is detected on an MHC.
What information does all the MHC molecules carry?
A map of all the self peptides in the body.
What is the immunological advantage of being able to define self?
The immune system can identify novel antigens/pathogens that have never existed before due to MHC presentation.
What is the peptidome?
All the peptides that are meant to be in the body.
What is the function of the peptidome?
To keep the T cells recognising and tolerating self peptides in-order for them to be able to distinguish foreign antigens
Important components of MHC1 processing: Proteases
- They break down large proteins into small peptides that can be presented as antigens.
- work in the proteasome
Important components of MHC1 processing: Adjacent proteins
- These allow or aid the binding of the peptide into the MHC.
- Chaperones like calnexin and calreticulin
- Transporter proteins like TAP
- Membrane loading complexes
What cells express MHC1?
All nucleated cells all of the time
What is the process of peptide loading into MHC1?
- The protein is tagged for degradation by ubiquitin.
- Degraded by protease activity.
- The peptide is exported to the ER.
- The peptide is loaded in the MHC1 with the aid of TAP.
- The peptide-MHC complex is transported to the cell surface in a vesicle.
Important components of MHC2 processing: HLA-DO and HLA-DM
These are chaperones that keep the MHC ready to receive peptides.