lecture 20 - t cell receptor activation

Question 1

What are the 3 signals involved in the control of T cell activation

Answer 1

Antigen specific TCR engagement
Contact with costimularory ligands
Positive sie CD28 which facilitate T cell activation
Negative CTLA-4 which turns T cell activation off
Cytokines directing Tcell proliferation and differentiation into effector subtypes

Question 2

Describe the adhesion step of T cell activation

Answer 2

Integrins (LFA-1) and Ig members (ICAM1, CD2, LFA3) interact
[LFA and CAM1]
[CD2 and LFA3]
CD4 and MHCCII → stabilized by the signalling molecule LCK and the zeta homodimer
CD22→ CD45
B7 → CD28

Question 3

Describe the immune synapse step of T cell activation

Answer 3

Receptors reorganize at the point of contact between T cell and APC, sets of adhesion complexes encircle TCR/MHC molecules
Increases avidity of T cell/APC interaction to provide structure for release of cytokine and initiating signalling
CSMAC→ central supramolecular activating complex (TCRMHC complexes and coreceptors centralize
PSMAC → peripheral supramolecular activating complex
Adhesion molecules bound ligands peripherally localize

Question 4

Describe the TCR signalling step of T cell activation

Answer 4

Initiated by
CD45R activating P56lck
CD28-B7 resulting in NF-kb activation
Which activate effector pathways 
CD8 → license to kill
CD4→ cytokine production

Question 5

What are the components of the TCR/CD3 complex, what purpose does it serve?

Answer 5

TCR, CD3 (2 epsilon, 1 delta and 1 gamma), zeta homodimer
Doesnt signal until TCR binds to antigen presented in MHC
ITAMS that contain tyrosine and phosporylated by kinases (LCK) and start the signalling cascade

Question 6

What role does LCK play in TCR signalling?

Answer 6

Kinase that associated with CD4 or CD8 and activated by CD45R
LCK phosphrylates ITAMS → docking sites for ZAP-70 which is also phosphorylatyed by LCK → phosphrylates PLC gamma
Plc gamma → increased calcium activates → calcineurin dephosphyrlates → NFAT (transcription factor) activation
PLC gamma → DAG secondary messenger → Protein kinase C→ NF-kB activation
Genes are expressed in response to said signalling