T cell receptor activation 2 Flashcards

1
Q

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

A

signal transduction proteins

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2
Q

What region of the TCR contain the complementarity determining region?

A

the variable region—it interacts with antigen/MHC

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3
Q

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

A

the V region

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4
Q

CDR3 is encoded by what region of the TCR?

A

The junction of V, D, and J

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5
Q

What does CDR1, CDR 2, and CDR3 specifically bind?

A

1=mostly MHC but partially antigen
2= almost entirely the MHC
3= almost completely the Antigen

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6
Q

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

A

Change conformation

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7
Q

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

A

False—It binds to both

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8
Q

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

A

No

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9
Q

Which CD co receptor is a monomer? a heterodimer?

A
monomer= CD4
heterodimer= CD8
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10
Q

Where do the CD4 and CD8 molecules bind on MHC?

A

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

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11
Q

Why is CD4/CD8 enhancement necessary?

A

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

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12
Q

Do TCR{ form homo or heterodimers?

A

homodimers

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13
Q

does CD3 epsilon form homo or heterodimers?

A

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

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14
Q

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

A

ITAM-immuno tyrosine based activation motifs yxxlx6-8yxxl

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15
Q

What initiates intracellular signaling from the TCR?

A

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

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16
Q

Zap-70 phosphorylates what?

A

LAT- form binding site for multiple signaling proteins

17
Q

What does PLC-gamma form by cleaving phosphatidyl inositol?

A

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

18
Q

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

A

LAT and recruits ITK

19
Q

What does PLC-gamma bind and what activates it?

A

LAT and phosphorylated by ITK

20
Q

What does PI3kinase do?

A

phosphorylates phosphatidyl inositol to form PIP3.

21
Q

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

A

Akt

22
Q

What does recruitment of GEF to LAT do?

A

stimulation of G proteins—>kinase cascades

ras>raf>mek>erk>TFs

23
Q

What pathway does calcium inflow cause?

A

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

24
Q

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

A

protein degradation

25
Q

Pathway of NF-kB activation?

A

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

26
Q

What does partial degradation of p100 lead to?

A

formation of p52

27
Q

Where do TFs bind to regulate genes?

A

promoter region

28
Q

What drives morphological changes in Tcell function?

A

actin polymerization and rearrangement—occur within minutes after activation

29
Q

What is Vav1?

A

GEF recruited by LAT

30
Q

What does Vav1 do?

A

Activates Rac, CDC42 and NCK.

31
Q

NcK binds to what>

A

WASp

32
Q

What does Rac/CDC42 and WASp lead to?

A

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