Linking: Signals 1 and 2

Question 1

Describe activation of t helper and cytotoxic T cells

Answer 1

Signal 1 = pmhc:Tcr (the cd binds constant region of mhc)
Signal 2= b7 on apc: cd28 on t cell
Signal 3= cytokines

Question 2

Name the 2 types of receptors

Answer 2

Extrinsic
Intrinsic

Question 3

Describe intrinsic receptors

Answer 3

Receptor itself has Intrinsic kinase activity
Signalling initiated by dimerization and transphosphorylation
Kinase domain = part of receptor

Question 4

Describe extrinsic receptors

Answer 4

Extrinsic kinase activity
Signalling initiated by RECRUITMENT of kinase and dimerization followed by transphosphorylation
Proteins recruited to receptor

Question 5

What are molecular interactions determined by

Answer 5

Protein binding domains in their structure that have selective binding properties

Question 6

Describe sh2 - molecule interactions

Answer 6

Sh2 domain = found in many proteins
Can recognize phosphorylated tyrosine on other proteins

Question 7

Describe phosphorylated tyrosines - molecule interactions

Answer 7

phosphorylated tyrosines = phosphotyrosines
=binding sites for a number of protein-interaction domains

Question 8

Describe result of molecule interaction

Answer 8

Leads to formation of multi molecular complexes around adaptor protein= once complete = then can have downstream effect

Question 9

Describe phosphorylation/ubiquitination

Answer 9

Key mods involved in signalling
Ub = usually for degradation but can activate
phosphorylation= activates proteins

Question 10

What are kinases

Answer 10

Proteins that phosphorylate other proteins —> lead to downstream cascade

Question 11

What are phosphatases

Answer 11

Proteins that dephosphorylate other proteins

Question 12

What happens to Ub proteins

Answer 12

Targeted for degradation usually by proteasome or lysosome

Question 13

What can ub/phosphorylation do

Answer 13

Activate or inhibit signalling
Signalling must be turned off and on = regulation at every step

Question 14

What is required for optimal T cell activation and proliferation

Answer 14

Costimulatory signals

Question 15

Describe signal 1

Answer 15

Pmhc:Tcr engagement with coreceptor binding

Question 16

Describe signal 2

Answer 16

Contact with costimulatory ligands
Also continues activation

Question 17

Describe signal 3

Answer 17

Cytokines directing T cell differentiation into distinct effector cell types

Question 18

Describe all signals

Answer 18

Result in intracellualr signalling = lead to change
Need all 3 signals to activation, proliferation and differentiation of T cells

Question 19

How does Tcr initiate signalling

Answer 19

Involves Tcr complex =
Tcr, itam domains, cd3 and zeta chains

Question 20

What happens when pmhc binds

Answer 20

When this occurs and coreceptor binds mhc (initiates first signal)
Binds constant region mhc = then lck

Question 21

What is lck - initiate signalling

Answer 21

A co receptor associated kinase recruited and will phosphorylate Itams = lead to more signalling
Lck = lymphocyte specific protein tyrosine kinase
Lck = already activated, needs to be activated before can do job

Question 22

What is zap-70 -initiate signalling

Answer 22

Recruited to itams and phosphorylated by lck
Zap70 binds to sh2 domain

Question 23

What does zap70 kinase do

Answer 23

Activates many downstream signalling molecules

Question 24

Describe whole process of Tcr signalling = series of events

Answer 24

Co receptor and Tcr binding —> lck recruited —> Itam phosphorylated — zap70 recruited —> Zap70 binds phosphorylated itams —> Zap70 phosphorylated —>downstream signalling effects

Question 25

is co receptor and lck intrinsic or extrinsic

Answer 25

Lck not apart of receptor = has to be recruited = therefore = EXTRINSIC

Question 26

Summarize signal 1

Answer 26

Bind peptide mhc Signal 1 results in intracellualr signalling = Lck recruited = phosphorylates itams Zap70 recruited and binds to phosphorylated itams Zap70 phosphorylated and leads to many signalling cascades downstream

Question 27

Signal 1 conclusions

Answer 27

Many pathways activated in parallel Leading to transcription of many gene s= for activation, survival and differentiation of T cells

Question 28

Why costimulation important t

Answer 28

Required for T cell activation, survival and proliferation

Question 29

Name costimulatory ligands on apc

Answer 29

Cd80 = b7.1 Cd86 = b7.2

Question 30

Name costimulatory ligands on Receptor on t clell

Answer 30

Cd28

Question 31

Name types of costimulatory receptors

Answer 31

Positive costimulatory receptors Negative costimulatory receptors

Question 32

Describe positive costimulatory receptors

Answer 32

Facilitate activation = cd28- receptor on T cells

Question 33

Describe negative costimulatory receptors

Answer 33

Help Turn activation off Ctla-4, pd1 Negative regulation

Question 34

What does anergy mean

Answer 34

Non responsive Anergic T cell =non responsive

Question 35

Describe cd28

Answer 35

Transmembrane glycoprotein expressed as a homodimer

Question 36

Where is cd28 found

Answer 36

On naive T cells AT BASELINE

Question 37

What does cd28 bind

Answer 37

B7.1 = CD80 & B7.2=CD86

Question 38

Describe cd80 and cd86

Answer 38

Homodimers Both expressed by activated professional apcs

Question 39

What type of interaction is cd28

Answer 39

Extrinsic bc need to recruiter pi3k = kinase, sh2 domain too Not part of receptor

Question 40

Describe whole process of cd28= 4 steps

Answer 40

1= binding to b7 molecules (cd80/86) 2=triggers phosphorylation of cd28 receptor by a kinase 3=recruitment of another kinase 4=additional signalling

Question 41

What is needed for mhc molecules to be effectively expressed on cell Surface

Answer 41

Need peptide bound to them first

Question 42

What happens if no costimulation

Answer 42

T cells become anergic Not just neg regulation - not the same

Question 43

Describe when clonal anergy

Answer 43

If no costimulatory signal Important in regulation and decrease the probability of auto reactive T cells (decrease/regulate this)

Question 44

T or F = anergic t cells can return to normal state and later response to costimulation

Answer 44

FALSEEEEEEEE Anergic T cell can no longer respond to stimulation = it’s forever, will never go back