Lecture 9 and 10: Dendritic Cells, MHC and Antigen Presentation Flashcards
What presents antigen to CD4+ helper T cells ?
Antigen presentation cells
What are the most efficient antigen presenting cells ?
Dendritic cells
What does antigen uptake by a dendritic cell result in?
Naive T cella activation; clonal expansion and differentiation into effector T cells
What does antigen uptake to macrophage result in ?
Effector T cell activation; activation of macrophages
What does antigen uptake in B cells result in ?
Effector T cell activation; B cell activation and antibody production
What are the different ways in which pathogens can replicate ?
- Cytosolic
- Intravesicular
- Extracellular
How do dendritic cells present peptide antigen to CD4 T cells ?
Through MHC II receptors
What allows it to bind and present antigen at cell surface ?
MHC structure
Where are MHC II molecules synthesised ?
ER
What prevents binding of MHC II in the ER ?
Ii
What does the invariant chain form ?
A complex with MHC II, blocking the binding of peptides and misfolded proteins
Where is Ii cleaved ?
In an acidified endosome
What is left in an acidified enzyme ?
Leaving a short peptide fragment, CLIP, still bound to the MHC II molecule
Where is the exogenous antigen processed ?
Endosomes
What binds to the MHC II releasing CLIP ?
HLA-DM
What is HLA-DM ?
Class II like molecule encoded for MHC region
Where is HLA-DM found ?
MIIC
What is the function of HLA-DM ?
- Binds and stabilises empty class II molecules which would otherwise aggregate
- Catalyses release of MHC from MHC CLIP complex
- Catalyses binding of peptide to empty MHC II
- Peptide edits
What sort of chains does HLA-DM have ?
Alpha and beta
What does HLA-DO do ?
Inhibits HLA-DM catalysed reaction
What increases HLA-DM expression ?
IFN-gamma
What happens during inflammation (to do with HLA-DM)
HLA-DM overcomes HLA-DO
What is APC activation of CD4 T cells good for ?
Cell mediated immunity and production of antibodies to fight extracellular bacteria or intravesicular infections
What are the three signals required for antigen presentation ?
- MHC specificity
- Costimulation
- Cytokines
What is costimulation ?
Control check to avoid over activation
What is anergy ?
Try to activate cells but do not have the right signal
How do viruses replicate ?
Intracellularly in the cytosol using endogenous protein synthesis machinery
What can kill virally infected cells ?
Activation of CD8 T lymphocytes
Where is MHC II only expressed ?
antigen presenting cells
Where is MHC I expressed ?
On all nucleated cells
What domain binds to CD8 co-receptor ?
Alpha 3 domain
What are the domains in the MHC I molecule ?
- Alpha 2
- Alpha 3
- Alpha 1
- Beta microglobulin
How do you get pathogen derived peptie loaded into MHC I ?
- Partly folded MHC I alpha chains bind to calnexin until Beta 2 microglobulin binds
- MHC I alpha: Beta2m complex is released from calnexin, binds a complex of chaperone proteins and binds to TAP via tapasin
- Cytosolic proteins are degraded to peptide fragments by the proteasome
- TAP delivers a peptide that binds to MHC I and completes its folding
- The fully folded MHC I is released from TAP and exported
What size peptides to MHC I bind ?
Short 8-10 amino acids long
What is binding of a peptide stabilised by ?
Contacts between atoms at carboxy and amino terminal ends of peptide and invariant sites on end of MHC I peptide binding groove
What does MHC I bind ?
Many different peptides but with common anchor residues
What is needed for efficient activation of CTL ?
APC co-stimulation
Where do naive CTL see viral antigen presented by MHC I ?
Cross presentation of viral antigen to CD8 T cells by APC
What is peptide loading in the ER targeted by ?
Viral immunoevasions
How do viral evasions US6 and ICP 47 block antigen presentation ?
By preventing peptide movement through TAP peptide transporter
What type of genes does MHC have ?
Polygenic and polymorphic
What type of specificity do TCRs have ?
Dual specificcity for MHC and peptide
