Linking: T cell proliferation

Question 1

When does hla-dm know when clip should be released

Answer 1

Ph drops even further = v low ph, hla-do = active in v acidic environment
= changes conformation of mhc 2 to release clip = allows peptide to load into peptide binding cleft

Question 2

Describe vesicle fusion specific for mhc 2 and peptide vesicles

Answer 2

Tethering (li) and snare proteins —> responsible for recognizing binding to proteins on target vesicles
Ex= mhc2 containing vesicles have specific snares that interact with those on antigen containing vesicles
Other molecules involved = cathepsins, rab gtpases

Question 3

What is needed for full activation of T cells

Answer 3

Signal 1 and 2

Question 4

What is important for survival of T cells

Answer 4

Il2

Question 5

What does il2 induce

Answer 5

Cytokine needed for clonal expansion = T cell has to make clones of itself = PROLIFERATION

Question 6

Describe what type of signalling il2 is

Answer 6

AUTOcrine cytokine response system
= T cells produce cytokine and receptor for il2, il2 binds receptor on cell that produced it

Question 7

What happens when il2 binds

Answer 7

Binding of this ligand induces a very strong proliferation signal during its activation stages

Question 8

What is outcome of il2 binding

Answer 8

Activation and robust proliferation
Production of memory (some) and effector (E) clonal cell populations

Question 9

Describe signal 1 and 2 converging - gen

Answer 9

Need both for T cells to activate transcription of il2 gene and transcription of il2Ralpha gene

Question 10

What happens after signal 1 and 2

Answer 10

Activation of transcription of il2 gene (cytokine) and il2Ralpha (part fo receptor)

Question 11

Is il2Ralpha gene expressed at baseline

Answer 11

NOOOOOO

Question 12

Are il2 and il2Ralpha on the same gene

Answer 12

Nooo 2 separate genes
transcription of these genes regulated diff

Question 13

Describe cascade = il2 and il2Ralpha

Answer 13

Signal 1 (tcr) and signal 2 (cd28) are required to initiate downstream signalling cascade —>activation of tfs that will bind to il2/il2Ralpha gene promoters = activates these genes = production of il2 and il2Ralpha

Question 14

Describe il2 receptor

Answer 14

Made up of 3 subunits =
Alpha
Beta
Gamma

Question 15

Are any parts of il2 receptors expressed at baseline

Answer 15

Yes
Il2R beta gamma chains are constitutively expressed on cell surface - of naive T cells

Question 16

Describe il2receptors and affinity

Answer 16

Baseline = il2R beta gamma = low affinity for il2 = not enough to proliferate cell
When il2Ralpha available = affinity of receptor for il2 increases = much higher = lead to sufficient proliferation and survival of T cell

Question 17

Describe resting/naive T cell - in context of il2

Answer 17

No il2
No il2Ralpha (has beta and gamma chains tho)

Question 18

Describe T cell after signals 1 and 2 - in context of il2

Answer 18

Transcription of il2 and il2Ralpha genes (binds rest of il2 receptor = beta and gamma chains)
Il2 secreted
High affinity il2R EXPRESSED

Question 19

What happens when il2 binds il2receptor

Answer 19

SIGNALLING from il2R results in proliferation and can help modulate T cell differentiation for some T cell subsets

Question 20

Can il2 only act in autocrine manner

Answer 20

NAWWW
Autocrine fashion primarily but
Can also act in paracrine fashion for tregs

Question 21

Describe tregs

Answer 21

Regulatory T cells
Sink - sponge for il2 to limit availability to other cells
Regulate cell mediated immunity
Tregs do not produce own il2 (=paracrine) but have il2Ralpha chain on their il2R (takes up il2 in environment to regulate)

Question 22

Il2Ralpha =

Answer 22

CD25