L6 - Cellular responses Flashcards
What do TCRs recognise?
Peptide fragments of foreign proteins
What do CD4 T cells recognise?
Antigens presented on the surface of professional antigen presenting cells (APCs)
What do CD8 T cells recognise?
Antigens presented on the surface of all nucleated cells
Describe the structure of a TCR
Made of one alpha chain, one beta chain. Each has a variable region (V), constant region (C), hinge (H), transmembrane region and a cytoplasmic tail. The tails are joined by a disulphide bond.
What is the purpose of the positive charge on the membrane spanning region of the TCR?
To balance the negative charges on the CD3 components and zeta chains
How many TCRs, CD3 components and zeta chains associate?
2 of each.
Which part of the TCR is responsible for the signalling?
The ITAMs (Immuno-receptor Tyrosine-based Activation Motif)
What mechanisms generate diversity in TCRs?
Somatic recombination between V, D, J (Beta chain) and V, J (alpha)segments. Also junctional diversity due to imprecise joining and addition of nucleotides by TdT
What is the structural difference between MHC class 1 and MHC class 2?
MHC class 1 is made of only an alpha chain, MHC class 2 made of alpha and beta chain
What stabilises the MHC class I molecule?
The association of a beta2-microglobulin
What is the difference in membrane spanning regions between each MHC class?
MHC I has 1 memb spanning region while MHC 2 has 2 memb spanning regions
Which portions of the TCR recognise the peptide presented by MHC
Hypervariable loops / complementarity determining regions (CDRs)
Which MHC does the co-receptor CD8 work with and what does it bind to?
CD8 is a co-receptor for the TCR and binds to the alpha3 subunit of the MHC I
Which MHC does the co-receptor CD4 work with and what does it bind to?
CD4 is a co-receptor for the TCR and binds to the beta2 subunit of the MHC II
Functions of T helper cells (expressing CD4)
Cytokine production, macrophage activation, “help” for B cells, cytotoxic T cell responses
Functions of T cytotoxic cells (expressing CD8)
Cytotoxic lysis of infected tumour cells
Where do the peptides originate when presented by MHC I
Cytosolic antigens (endogenous pathway)
Where does the assembly of peptide-class 1 complexes occur?
In the ER
What is the function of calnexin?
Chaperone which binds alpha chains until beta2-microglobulin binds
Which cells is the MHC class II pathway limited to
Professional antigen presenting cells
In the MHC class II pathway what is the origin of the antigens?
Extracellular or vesicular - exogenous pathway.
List the three professional antigen presenting cells
Dendritic cells, macrophages and B cells
What is the central chaperone for the class II pathway?
The invariant chain (Ii)
What is the role of HLA-DM?
It binds to the MHC II molecule, releasing CLIP (the remnant of the invariant chain, Ii) and allowing other peptides to bind. The MHC II molecule then travels to the cell surface.
Name ways that dendritic cells can take up antigens
Macro-pinocytosis, receptor mediated endocytosis, viral infection
Which three signals from APCs do naïve T cells receive (in the blood)?
Signal 1 - Activation - TCR and CD4 co-receptor bind to MHC class II Signal 2 - Survival - costimulatory molecules B7.1 (CD80) and B7.2(CD86) interact with co-stimulatory receptor CD28 on T cell surface Signal 3 - Differentiation - variety of cytokines eg IL-1, IL-12
What determines the which T cell subset will be produced?
The various cytokines produced by APCs
List the fate determining cytokines and state which cell types they determine.
IFN-gamma + IL-12 produce Th1 cells IL-4 produces Th2 cells TGF-beta + IL-6 + IL23 produce Th17 cells IL-6 produces Tfh cells TGF-beta + IL-2 iTreg cells
