T cell receptor activation 2 Flashcards Preview

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Flashcards in T cell receptor activation 2 Deck (32):
1

What type of proteins of the 435 proteins drugs target are the most common?

signal transduction proteins

2

What region of the TCR contain the complementarity determining region?

the variable region---it interacts with antigen/MHC

3

CDR1 and CDR2 are encoded by what region of the TCR>

the V region

4

CDR3 is encoded by what region of the TCR?

The junction of V, D, and J

5

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

6

What can DR3 do whether it is bound to or unbound ?

Change conformation

7

T-F, The antigen/MHC complex only binds to the TCR and not to CD4/CD8?

False---It binds to both

8

Does the TCR and CD4/CD8 that are bound to the same antigen/MHC complex associate with each other?

No

9

Which CD co receptor is a monomer? a heterodimer?

monomer= CD4
heterodimer= CD8

10

Where do the CD4 and CD8 molecules bind on MHC?

invariant regions distant from the cleft---they greatly enhance the sensitivity

11

Why is CD4/CD8 enhancement necessary?

low number of MHC/antigen complexes on the cell that a single TCR can interact with needsenhancement

12

Do TCR{ form homo or heterodimers?

homodimers

13

does CD3 epsilon form homo or heterodimers?

heterodimer with gamma on one side and with delta on the otehr

14

What do the CD3 subunits and the TCR{ subunits contain?

ITAM-immuno tyrosine based activation motifs yxxlx6-8yxxl

15

What initiates intracellular signaling from the TCR?

phosphorylation of ITAMS by tyrosine kinase LcK----> recruit and bind zap-70

16

Zap-70 phosphorylates what?

LAT- form binding site for multiple signaling proteins

17

What does PLC-gamma form by cleaving phosphatidyl inositol?

diacylglycerol for PKC or inositol 1,4,5 phosphate for Ca influx
(DAG and IP3)

18

What does SLP-76 bind and what does it recruit?

LAT and recruits ITK

19

What does PLC-gamma bind and what activates it?

LAT and phosphorylated by ITK

20

What does PI3kinase do?

phosphorylates phosphatidyl inositol to form PIP3.

21

What very important downstream regulator of activity, cell survival, apoptosis, translation, TF activation and metabolism is activated by PI3 kinase?

Akt

22

What does recruitment of GEF to LAT do?

stimulation of G proteins--->kinase cascades
(ras>raf>mek>erk>TFs)

23

What pathway does calcium inflow cause?

Ca>binds calmodulin> binds calcineurin> dephosphorylates NFAT a TF>>nuclease to drive transcription

24

What is critical for the activation of the NF-kB pathway

protein degradation

25

Pathway of NF-kB activation?

DAG>IKK complex> phosphorylate I-kB> I-kB is degraded> releases NF-kB

26

What does partial degradation of p100 lead to?

formation of p52

27

Where do TFs bind to regulate genes?

promoter region

28

What drives morphological changes in Tcell function?

actin polymerization and rearrangement---occur within minutes after activation

29

What is Vav1?

GEF recruited by LAT

30

What does Vav1 do?

Activates Rac, CDC42 and NCK.

31

NcK binds to what>

WASp

32

What does Rac/CDC42 and WASp lead to?

Arp2/3-->actin branching (mutations in any of these causes sever Tcell defects)