Antigen presentation Flashcards
Describe the function of dendritic cells
They report the site of infection; the innate dendritic cell takes the infection to Lymph node; the sensing of pathogen triggers cell migration via lymphatic vessels.
In the Lymph node, dendritc cells present MHC/peptide to naive T cells which stimulates Adaptive response and relays information to T cells.
This causes the effector T cells to activate and travel to the infected tissue to engage other cells presenting the same antigen used to stimulate T cell.
Describe the function of dendritic cells
They report the site of infection; the innate dendritic cell takes the infection to Lymph node; the sensing of pathogen triggers cell migration.
In the Lymph node, dendritc cells present MHC/peptide to naive T cells which stimulates Adaptive response and relays information to T cells.
This causes the effector T cells to travel to the infected tissue to engage other cells presenting the same antigen used to stimulate T cell.
T cells activate antibodies.
Antibodies recognize lipids, carbohydrates, lipids, proteins, nucleic acid
T cells recognise in a different way; to make antibodies, T cells must recognise the antigen
Difference between T cells and B cells recognition.
Antibodies recognize lipids, carbohydrates, lipids, proteins, nucleic acid on the folded pathogen not broken down.
T cells recognise in a different way through unfolded PEPTIDE fragment and MHC; to make antibodies, T cells must recognise the antigen
What kinds of information does the dendritic cell give to T cell?
processed pathogen fragments presented via MHC on cell surface.
What does antigen processing inside dendriic cell refer to?
The pathogen protein is unfolded chopped into smaller fragments. They bind to MHC and travel to cell surface for presentation.
T cells must see this before they can be activated.
What is the difference between the classes of MHC?
Class 1: presents to CD8+ T cells. his alerts to intracellular infection of viruses.
Class 2: presents to CD4+ T cells.
MHC molecules. What are the characteristics
Major Histocompatibility complex.
Chromosome 21 on mouse locus that controlled mouse rejection and skin graph rejection due to immune response; inflammation ect via foreign T cell activation..
Therefore, MHC genes are very polymorphic, they are different in everyone causing incompatibility.
What is the difference between the classes of MHC?
Class 1: presents to CD8+ T cells. MHC 1 is bound to all cells. This alerts to intracellular infection of viruses as foreign/ENDOGENOUS peptides are captured and loaded on MHC in the E.R. They follow secretory pathway to cell surface and present to killer T cells in cytoplasm.
Class 2: presents to CD4+ T cells. This alerts to EXTRACELLUALR infection of bacteria where B cells, dendritic cells and macrophages engulfs and degrades bacterium into peptides, loads into MHCII in vesicles and presents to helper T cells. So they can activate the Antigen Presenting Cell.
What cells have MHCI ?
All cells; as all cells can become virally infected.
What cells have MHCII?
B cell, macrophages, dendritic cells.
These cells are then activated by correct helper T cell to kill via the APC’s effector function
Difference between T cells and B cells recognition.
B cells and their Antibodies can recognize lipids, carbohydrates, lipids, proteins, nucleic acid on the folded pathogen not broken down. (any chemical structure)
T cells recognise in a different way through unfolded PEPTIDE fragment and MHC; to make antibodies, T cells must recognise the internal antigen peptides
T cells recognise other host cells (showing foreign infection) ; B cells recognise a free foreign antigen
How is the relationship between B cell and T cells important in vaccines
Part recognised by the B cell is physically linked to the part/peptide fragment recognised by the T cell once it has been processed by the infected cell.
Describe the appearance of MHCI and MHCII in terms of their crystal structures
- MHC1 has SINGLE transmembrane chain = alpha chain is divided into 3 domains: a1, a2, a3. B2 Microglobulin stabilises structure.
- MHC2 has one transmembrane chain= the alpha chain is divided into 2 domains: a1, a2.
Structure is similar, although chains are different where two long alpha helices in MHC1, and one alpha and one beta long helices in MHC2 form the peptide binding site/groove.
What is a difference between MHCI and MHCII crystal structures?
The terminals of peptide (N and C) engages in specific interactions with MHC1 so there is a SIZE limit of how many peptide residue there are.
Terminal do not interact with MHCII terminals.
What holds the peptides in the grooves of MHC molecules?
They are held stably by HYDROGEN BONDS and charge-charge interactions on the backbone on the peptide.
On the backbone C=O and N-H make hydrogen bonds on the side chain.
The fit is very precise: peptide side chains fit into MHC pockets and some side chains are required to be specific aa to be in pocket.
What is a difference between MHCI and MHCII crystal structures?
The terminals of peptide (N and C) engages in specific interactions with MHC1 so there is a strict SIZE limit of how many peptide residue there are: 8-10 aa
C terminal aa of MHC1 peptides are basic or hydrophobic
Terminal do not interact with MHCII terminals where peptides come out at either side of MHC so no limit to aa length; usually 12-24
What does promiscuous peptide binders mean?
One MHC molecule can bind to thousands of different peptides
Describe the cell in terms of topological domains
1) cytosol (continuous with nucleus and rest of cell without membrane barrier) MHCI: they are loaded in E.R in the secretory pathway
2) vacuolar where external environments can enter the cell. MHCII: vesicles are key for loading reactionwhere endocytic vesicle with antigen is degraded and fused with vesicle of MHCII where it is loaded.
How does inflammation differ MHC loading of peptides?
Interferon-gamma (IFN-gamma) produced changes conformation of the proteasome (MHC1 pathway)
How does inflammation differ MHC loading of peptides? What is an immunoproteasome?
Interferon-gamma (IFN-gamma) produced changes conformation of the proteasome (MHC1 pathway)
This causes alternative subunits to make up proteasome, producing an immunoproteasome. This makes peptides more suited to MHC1 binding requirements at the C terminal.
What is TAP?
Transporter Associated with antigen Processing which delivers peptides to E.R
Describe the Peptide loading complex (PLC) in terms of MHC1
It organises the MHC1 assembly using various chaperone helpers.
1) Calnexin stabilises heavy chain. It leaves after B2 microglobulin binds.
2) the alpha hetrodimer and B2 form the loading complex (PLC) including TAP protein, , tapasin (links MHC1 to TAP so they are in correct location), calreticulin, ERp57, PDI.
3) Peptides from proteasome through TAP where the MHC1 can sample the peptides for correct binding.
4) Binds and MHC1, edited by ERAP and leaves ER and PLC
Which chaperone is important for MHC1 and peptide association
Tapasin; needed for MHC sampling and rejection of peptides.
Tight binding may take several attempts.
What is meant by a first draft of a peptide?
Proteasome make a “first draft” peptide where C terminus is correct due to immunoproteasome.
Where the peptide is too long at the N terminus so ERAP aminopeptidase removes aa from N terminal to produce peptide of 8-10aa length.
What are the generic protein chaperones and dedicated chaperones involved in PLC?
generic:
- calnexin
- calreticulin
- ERp57
- PDI
Dedicaed:
- TAP,
- Tapasin
- ERAP
What is bare lymphocyte syndrome?
Where the TAP is absent and so 1% of MHC1 present on cell surface (missing MHC1) so poor virus response as T cell are not activated.
Viruses can make proteins that block TAP causing similar effect.
Deficencies in any chaperone defects peptide loading and means abnormal CD8+ response.
What is the function of the invariant chain in MHC2 loading?
It blocks binding of peptides to MHC2 within the ER.
It also acts as a targeting subunit so MHC2 is targetted across to endocytic/vescicle pathway.
