TCR signalling Flashcards
what is signal transduction?
conversion of energy or information from one form into another
what are the steps in signal transduction?
- extracellular molecule activates a cell surface molecule
- this receptor alters intracellular molecules
- amplification of the signal
what is the result of signal transduction?
ultimately, get gene transcription and protein production
what are the first messengers in signal transduction?
-natural inter-cellular ligand that bind and activate receptors
- need receptors in the membrane
what is the role of the second messengers in signal transduction?
-enter the cytoplasm and trigger response within the cell
- chemical relays from plasma membrane tp cytoplasm
- intracellular signal transduction
what determines what happens inside a target cell?
external influences,
need receptors in the membrane
what is the function of downregulation?
avoid persistent activation
what is affinity?
strength of binding
what is avidity?
strength of interaction
what is the structure of the T cell receptor?
Two chains- alpha and beta
Variable region and constant region
Membrane bound only
what molecules are involved in signal one of T cell activation?
Antigen-specific
- TCR and MHC
what molecules are involved in co-receptor during T cell activation?
CD4/8
MHC
what molecules are involved in adhesion during T cell activation?
LFA-1
ICAM
what molecules are involved in signal two of T cell activation?
CD28
CD80
what molecules are involved in inflammatory signals in T cell activation?
APC
IL-12
what is antigen specific binding in T cell activation?
TCR and MHC bind
- T cell recognizes specific antigen
what is the co-receptor stage in T cell activation?
CD4 MHCII
CD8 MHCI
stabilise low-affinity interaction between TCR and MHC
Co-receptor stabilizes cell-to-cell binding
what is the adhesion stage in T cell activation?
LFA-1 on T cells
ICAM-1 on APC
stabilise interaction between T cells and APCs
Adhesion molecules further stabilise cell-to-cell binding
what is the co-stimulation stage in T cell activation?
Signal 2
-CD28-CD-80 interaction
Costimulatory receptor sends extra activation signal
What are the intracellular signalling stages in T cell activation?
- Phosphorylation of ITAMs
- co-receptor signal
- activation of ZAP-70
- involvememt of scaffold proteins and adaptor molecules
- activation of PLC-y
- activation of transcription factors
how are ITAMs phosphorylated?
Two tyrosine kinases phosphorylate ITAMS
what happens when ITAMs are phosphorylated?
It exposes their active sites
- Lck becomes constitutively associated with cytoplasmic domains of CD4 and CD8
- Fyn associates weakly with cytoplasmic chains of x and CD3 chains
what is the co-receptor signal in intracellular T cell activation?
CD4 and CD8 involved
- brings Lck associated with co-receptor together with ITAMs
how id ZAP-70 activated?
Phosphorylated ITAMs provide a binding site for ZAP 70
ZAP 70 gets phosphorylated by Lck
what is the role of phosphorylated ZAP-70?
activated ZAP-70 phosphorylated scaffold proteins LAT and SLP76
These recruit phospholopase PLC-g
what is the role of LAT and SLP76 scaffold proteins?
recuit PLCg to the membrane
It is recruited to the signalling complex and then phosphorylated by Lck
what is the role of activated PLCg?
PLC activation leads to three pathways that activate distinct transcription factors
what is the outcome of activating transcription factors in intracellular T cell activation?
Transcription factors regulate gene expression
IL-2= T cell proliferation and survival
Performin/granzyme= T cell cytotosic function
Cytokines= activate other cells depending on type of infection
