Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

micr 386 > module 04 section 03 (TCR activation) > Flashcards

module 04 section 03 (TCR activation) Flashcards

1
Q

following antigen processing, peptides are:

A

stably bound to the polymorphic aa anchor residues within the MHC binding cleft for antigen presentaion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

recall: do T-cells have single or dual specificity?

A

dual:

  • the CDR1/2 of the TCR bind to the polymorphic residues of self-MHC molecules
  • CDR3 of the TCR binds to the specific residues of the peptide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

with respect to TCR, what is a crucial step of T-cell activation?

A

the specific binding of TCR to the MHC:peptide complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what signals does a naive T-cell require to become fully activated?

A

a pre-signal and 3 extracellular signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what must occur for the 3 extracellular signals to occur?

A

the T-cell and APC need to be close in proximity, which involves adhesion of the helper T-cell to the APC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

the helper T-cell adheres to the APC through?

A

the binding of adhesion molecules:

  • CD2/LFA-3
  • LFA-1/ICAM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is CD2? where is it found?

A

cell adhesion molecule found on the surface of T-cells and NK cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is LFA-3? where is it found?

A

cell adhesion molecule expressed on antigen presenting cells, particularily macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is LFA-1? where is it found?

A
  • cell adhesion molecule found on lymphocytes

- plays key role in emigration (process of leaving the bloodstream and entering tissue)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is ICAM-1? where is it found?

A

cell adhesion molecule expressed on antigen presenting cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is done to stabilize the adhesion process of T-cells to APCs?

A

the CD4 coreceptor binds to MHC class II on the APC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what family of molecules does LFA-1 belong to?

A

integrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what family of molecules does LFA-3 belong to?

A

Ig superfamily

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

recall: what is the pre-signal?

A

adhesion of helper T-cell to the APC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is the 1st extracellular signal?

A

antigen recognition:

  • TCR recognizes the peptide:MHC complex
  • this low affinity TCR-MHC interaction is stabilized by the adhesion molecules which form a synapse
  • the synapse consists of the adhesion molecules moving and encircling the TCR-peptide:MHC complex for ~10 mins
  • each peptide:MHC complex can sequentially engage w up to 200 TCRs on a T-cell in a process called serial triggering
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is the 2nd extracellular signal?

A

co-stimulatory molecules:

involves the binding of (non-specific) costimulatory molecules B7/CD28 or CD22/CD45R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is B7? where is it found?

A
  • proliferatory membrane protein found on activated antigen presenting cells
  • there’s two types: B7-1 and B7-2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is CD28? where is it found?

A

protein expressed on T-cells that provides co-stimulatory signals that provide T-cell activation and survival

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is CD22? where is it found?

A

sugar binding transmembrane protein that binds sialic acid and functions as an inhibitory receptor for B-cell receptor signalling
found on the APCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is CD45R? where is it found?

A
  • member of the protein tyrosine phosphatase fam

- expressed on B-cells at all developmental stages and some T-cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

do APCs have similar or differential expression of co-stimulatory signals?

A

differential

22
Q

describe the expression of co-stimulatory signals for dendritic cells

A

consecutive expression of B7

constantly expressed on the cell surface

23
Q

describe the expression of co-stimulatory signals for macrophages

A

inducible expression of B7

24
Q

describe the expression of co-stimulatory signals for B-cells

A

inducible expression of B7

25
can co-stimulatory singals be excitatory? inhibitory?
yes for both
26
what differentiates B7-1 from B7-2?
B7-2 expresses an intracellular phosphate group
27
the binding of B7-1 to CD28 elicits _____ signals
stimulatory
28
the binding of B7-2 to CTLA-4 elicits _____ signals
inhibitory
29
what is the 3rd extracellular signal?
effector cell function: - involves preformance of the cell effector function - TCR activation induces helper T-cells to produce cytokines that perform the effector function of the T-cell - same thing occurs for cytotoxic T-cells
30
what is the result of successful extracellular signalling?
the promotion of a cascade of intracellular signalling to activate T-cells through the TCR/CD3
31
what are tyrosine-based activation motifs (ITAMs)?
conserved sequences contained by the cytoplasmic domains of CD3 molecules
32
what do ITAMs contain? | what role do these play?
ITAMs contain tyrosine residues that are phosphorylated by protein tyrosine kinases
33
of all of the TCR/CD3 complexes, how many are homodimers and how many are heterodimers?
90% homo (ζ,ζ) | 10% hetero (ζ,η)
34
recall: what are the key players in intracellular singalling of the TCR/CD3 complex? (2)
tyrosine kinases and phosphatase
35
what is a kinase?
enzyme that catalyses the transfer of a phosphate group from ATP to a specific molecule
36
what is a phospatase?
enzyme that catalyses the hydrolysis of organic phosphates in a specified environment
37
what are the specific tyrosine kinases involved in intracellular signalling? (3)
ZAP-70 Fyn Lck
38
what is ZAP-70?
protein normally expressed near the surface membrane of T-cells
39
what is Fyn?
- protein tyrosine kinase | - involved in the regualtion of cell morphology
40
what is Lck?
- protein tyrosine kinase found in T-cells | - most commonly associated with cytoplasmic tails of CD4 and CD8 co-receptors
41
what is step 1 of intracellular singalling for TCR activation?
- simultaneous binding of TCR and CD3 to the peptide:MHC complex results in the close proximity of Lck and Fyn on the ITAMs of CD3 - the kinases are unable to phosphorylate the ITAM tyrosine residues due to the presence of inhibitory phosphate grps
42
what is step 2 of intracellular singalling for TCR activation?
- binding of CD22 to CD45R activates the protein tyrosine phosphatase on the cytoplasmic tail of CD45R - the phosphatase cleaves the inhibitory phosphate grps on Lck and Fyn
43
what is step 3 of intracellular singalling for TCR activation?
activated Lck and Fyn kinases phosphorylate the ITAM residues on CD3-ζε
44
what is step 4 of intracellular singalling for TCR activation?
the phosporylated CD3ζ chain ITAM residues act as docking sites for ZAP-70, allowing it to bind to CD3ζ and become activated
45
what is step 5 of intracellular singalling for TCR activation?
activated ZAP-70 and fyn kinases phosphorylate phospholipase C-γ1 (PLC-γ1) in the plasma membrane of the T-cell
46
what is step 6 of intracellular singalling for TCR activation?
acitvated PLC-γ1 cleaves phosphatidylinositol-4-5-biphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG) - which activate transcription factors, NF-AT and NF-kB, respecitvely
47
what is step 7 of intracellular singalling for TCR activation?
- IP3 diffuses through the cytoplasm and binds to IP3-sensitive Ca channels, releasing intracellular Ca stores - increased intracellular Ca concentration promotes protein kinase C expression on the plasma membrane - prot. kinase C expressed on plasma membrane can be activated by DAG
48
what is step 8 of intracellular singalling for TCR activation?
- the increase of intracellular ca from the activation of IP3 sensitive CA channels also promoted binding of Ca to calmodulin - calmodulin then activates calcineurin phosphatase which dephosorylates a family of transcription factors, including NF-AT - NF-AT translocates into the nucelus and binds to the NF enhancer region on the IL-2 gene
49
what is step 9 of intracellular singalling for TCR activation?
- prot kinase C activated by DAG phosphorylates an inhibitory factor, releasing transcription factor NF-kB - NF-KB then translocates to the nucleus and dimerizes with another IL-2 enhancing region
50
recap: what does the TCR signalling cascade ultimately lead to?
the enhanced transcription of the IL-2 gene
51
the production of IL-2 within the activated T-cell promotes what?
proliferation and differentiation of the T-cell into effector and memory T-cells

micr 386 (31 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions