T cell mediated Immmunity

Question 1

How do B and T cells differ in their recognition of an antigen

Answer 1

T cells- need antigen processed and presented on a APC (via MHC or HLA)
Cytosolic infections (virus) - presented on HLA I 
Vesicular intracellular pathogens- presented on MHC/HLA II

B cells- can bind to antigen through surface immunoglobulin

Question 2

Differences in B and T cell receptor

Answer 2

B cell receptor- surface immunoglobulin:

- 2 heavy and light chains with constant (constant between B cells) and variable (specific to epitope) domain 
- 2 combining site- made up of the variable heavy and variable light chain 
- Capacity to recognise different targets due to variability in variable domains 

T- Cell receptors

- Typical T cell receptors made up of a and b chain- with variable and constant domains- constant domains are closest to cell surface whereas variable domains bind to the target 
- Variable domains can bind to different antigens presented to them on MHC class I or II 
- T- cell receptor is like 1 arm of a B cell receptor so only has 1 antigen binding site  - Carbohydrates associated with variable and constant regions can have indirect binding with pathogen  - Hinge region consisting of disulphide bridge kinking a and B chain  - Anchored to cell vis transmembrane region  - Small cytoplasmic tail

Question 3

Explain structure of MHC class I and class II molecule and when they are used

Answer 3

MHC class I (intracellular cytosolic infection)

• Large alpha chain non-covalently associated with B2-microglobulin polypeptide (B2M)
• Type of immunoglobulin as a3 and B2M domain structurally homologous to immunoglobulin domain
• A1 and a2 domains form a cleft/ peptide- binding groove on surface distal to cell surface membrane so that it is available for interaction with TCR

HLA class II proteins: (intracellular vesicular infection)

• have 2 similarly sized polypeptide chains called class II a and b chains
• A2 and b2 domain proximal to cell surface and homologous to immunoglobulin- like domains
• A1 and b1 remain distal to cell surface and form peptide-binding cleft to hold the antigen peptide for recognition by TCR

Question 4

Overview- what happens in a cytosolic intracellular infection?

Answer 4

1) Antigen processing: Endogenous antigen (inside cell) is degraded in the cytosol by the proteasome into peptide fragments
2) Transported via peptide transporter into the ER
3) Peptide fragments are loaded onto MHC-1 newly synthesised in ER
4) MHC class 1 presents the processed antigens on the cell surface
5) The a3 domain on MHC class 1 will interact with the CD8 coreceptor on the CD8 cytotoxic T cell
6) Hence the cytotoxic T cell is activated and will phagocytose infected viral cell

Question 5

Overview- what happens in a intracellular vesicular infection (e.g. macrophage completed phagocytosis)?

Answer 5

1) Antigen degraded in vesicle (antigen processing)
2) MHC class 2 molecule made in ER and loaded in a vesicle
3) Invariant chain is bound to the binding groove in MHC class II in ER
4) This ensures that the HLA class II does not bind to the processed viral antigens in the ER
5) 2 vesicles bind in cytosol and HHC- II loaded in vesicle
6) Antigen presentation by MHC class II on cell surface
7) B2 domain of MHC class II binds to CD4 coreceptor on the CD4 Helper T cell
8) Activation of T cell helps macrophage to better intracellularly digest pathogen

Question 6

Explain 3 signals important in activation of T cells

Answer 6

1) Need T cell receptor for direct recognition- containing the a and b chains (containing constant and variable domains) - this specifically recognises the antigen that is being presented on MHC class I or class II
- CD4/CD8 is the coreceptor- CD4 is present on cytotoxic killer cell (which binds to MHC I) whereas CD8 is present on T helper cell (which binds to MHC II)- ensures correct T cell activated
2) B7 molecules expressed on the surface of APC and CD28 expressed on surface of T cell trigger signal 2 - to ensure cell doesn’t become anergic (don’t respond to antigen) and switch function off cell off
With these 2 signals T cell becomes activated to carry out its particular function
3) Cytokines- depending of the cytokines produced when T cell activated- influences the type of T cell response that we get