T cell activation

Question 1

TCR structure

Answer 1

hetero dimer with an alpha and beta chain
variable domain + constant domain for each chain
alpha = V, J and C
beta = V, D, J and C

Question 2

Somatic rearrangement

Answer 2

follows 12/23 rule
no change in TCR affinity during activation
shows allelic exclusion and the rearrangement
beta chain: only has two constant regions, one is selected and it doesn’t effect function
alpha chain: one constant domain

Question 3

Hypervariable region diversity

Answer 3

The first two regions are encoded in the germline, in the V region
- Mainly making contact with the MHC molecule
- Not black and white, can bind with peptide

The third region is formed by the junction of the V and the J -> makes the principle contacts with peptide MHC

Question 4

contact residues on peptide and TCR

Answer 4

more than four fold = more important for interactions, can’t handle mutations

Question 5

TCR signalling complex

Answer 5

coreceptors
- CD3
- zeta chains
both have ITAMs
needed for activation and stabilizing receptor

Question 6

Step 2 T cell activation

Answer 6

MHC binds to TCR. CD4 or 8 binds to MHC, bringing Lck into close proximity to ITAMs
Lck phosphorylates ITAMs

Question 7

Step 1 T cell activation

Answer 7

CD45 dephosphorylates Lck
Lck auto phosphorylates itself to perform kinase function

Question 8

Step 3 T cell activation

Answer 8

ITAMs act as docking sites for ZAP-70, which is activated by phosphorylation by Lck

Question 9

Step 4

Answer 9

ZAP-70 phosphorylates other proteins, leading to cytoskeleton rearrangements, transcription factor activation, increases integrin adhesion and metabolic activity

Question 10

What does ZAP-70 do

Answer 10

phosphorylate LAT and SLP-76, which are adaptor proteins

Question 11

what does PLC-gamma do/what does it need

Answer 11

it leads to transcription factor activation and needs CD28