T cell receptor activation 2 Flashcards
What type of proteins of the 435 proteins drugs target are the most common?
signal transduction proteins
What region of the TCR contain the complementarity determining region?
the variable region—it interacts with antigen/MHC
CDR1 and CDR2 are encoded by what region of the TCR>
the V region
CDR3 is encoded by what region of the TCR?
The junction of V, D, and J
What does CDR1, CDR 2, and CDR3 specifically bind?
1=mostly MHC but partially antigen
2= almost entirely the MHC
3= almost completely the Antigen
What can DR3 do whether it is bound to or unbound ?
Change conformation
T-F, The antigen/MHC complex only binds to the TCR and not to CD4/CD8?
False—It binds to both
Does the TCR and CD4/CD8 that are bound to the same antigen/MHC complex associate with each other?
No
Which CD co receptor is a monomer? a heterodimer?
monomer= CD4 heterodimer= CD8
Where do the CD4 and CD8 molecules bind on MHC?
invariant regions distant from the cleft—they greatly enhance the sensitivity
Why is CD4/CD8 enhancement necessary?
low number of MHC/antigen complexes on the cell that a single TCR can interact with needsenhancement
Do TCR{ form homo or heterodimers?
homodimers
does CD3 epsilon form homo or heterodimers?
heterodimer with gamma on one side and with delta on the otehr
What do the CD3 subunits and the TCR{ subunits contain?
ITAM-immuno tyrosine based activation motifs yxxlx6-8yxxl
What initiates intracellular signaling from the TCR?
phosphorylation of ITAMS by tyrosine kinase LcK—-> recruit and bind zap-70
Zap-70 phosphorylates what?
LAT- form binding site for multiple signaling proteins
What does PLC-gamma form by cleaving phosphatidyl inositol?
diacylglycerol for PKC or inositol 1,4,5 phosphate for Ca influx
(DAG and IP3)
What does SLP-76 bind and what does it recruit?
LAT and recruits ITK
What does PLC-gamma bind and what activates it?
LAT and phosphorylated by ITK
What does PI3kinase do?
phosphorylates phosphatidyl inositol to form PIP3.
What very important downstream regulator of activity, cell survival, apoptosis, translation, TF activation and metabolism is activated by PI3 kinase?
Akt
What does recruitment of GEF to LAT do?
stimulation of G proteins—>kinase cascades
ras>raf>mek>erk>TFs
What pathway does calcium inflow cause?
Ca>binds calmodulin> binds calcineurin> dephosphorylates NFAT a TF»nuclease to drive transcription
What is critical for the activation of the NF-kB pathway
protein degradation
