Advanced Antigen Presentation Flashcards
Are T cells able to recongise antigenic fragments bound to MHC molecules?
Yes
What are the three stages to T cell activation?
1) TcR:MHC
2) Costimulation
3) Cytokines
What does it mean when MHC are polygenic?
Multiple gens with the same function but different structures: broad rang of peptide binding specificities
What does it mean when MHC are polymorphic?
Multiple forms of each gene exist within the population
What does it mean when MHC are co-dominantly expressed?
Set of linked alleles inherited from paretns
What is the role of Calreticulin in the Peptide Loading Complex
- Maintain structure of MHC I
- Rtrieves unstable MHC molecules
What is the role of Tapasin?
1) Stabilises interaction between TAP1/2
2) Increases rate of peptide transport into ER
3) Bridges TAP1-MHC I
4) Assists loading of MHC I
What is the Invariant Chain process?
1) Bind to MHC II in peptide binding groove (prevents other peptides binding)
2) Motif that allows transfer of MHC II to other vesicles
What is a Cathepsins?
Degrade invariant chain and peptides
What is Endopeptidases?
Break bonds within proteins (including invariant chain to CLIP)
What is Exopeptidases?
Break bonds at the ends of proteins
What are the roles of the HLA-DM (Human lukocyte antigen DM)?
- Does not bind to peptides
- Promotes dissociation of CLIP
- Catalyses peptide exchange by holding MHCII ‘open’
What is cross-presentation?
Process through which exogenous antigen is sometimes presented with MHC class I
What is the two pathways in cross presentation?
1) Endosome to cytosol pathway
2) Vacuolar pathway
What is the Alternative antigen presentation?
Steal a pre-formed MHC/peptide complex from another cell
What is Trogocytosis?
Taking membrane components from another cell
What are the 3 ways of presentation?
- Direct presentation
- Cross presentation
- Cross dressing
What does cell activation do with lipid rafts?
Clustering of surface receptors into lipid rafts
What are rafts?
Detergent-insoluble sections of membrane, rich in cholesterol and lipids
What role does lipid rafts have?
Regulate activity of enzymes within them
What does lipid rafts come together to become?
Immune synapse
What are the main effects of the early immune synapse?
- Increases adhesion
- Targets cytokines and signalling between APC and T cell
- Greater induction of co-stimulatory signals (signal 2)
What is the Central Supra Molecular Activation Cluster (cSMAC)
TCR/CD3 microclusters (MC) and co-stimulatory molecules (e.g. CD28)
What is the Peripheral Supra Molecular Activation Cluster (pSMAC)?
LFA-1 is activated by TCR signals (inside-out signalling) and by binding ligand (ICAM-1; outside-in signalling); high affinity LFA-1 is now located in pSMAC
What is the Distal Supra Molecular Activation Cluster (dSMAC)?
Rich in CD45
- De-phosphorylates proteins
- Able to activate and inhibit aspects of T cell activation
What is the Kinetic segregation model?
CD45 is physically excluded from the central synapse
- Alters local blances of phosphatases
- Favours expression of kinases and therefore activation
What iss Cytotoxic SMAC?
- Synapse formed between CTLs and targets
- Enables targeted secretion of cytotoxic granules (containing granzymes and perforin)
What is Centrosome also known as??
Microtubule organising centre (MTOC)
What is the function of MTOC?
Reorientation of microtubules
