Linking Innate and Adaptive Immunity 6

Question 1

what occurs inside the cells when APC activates T cells?

Answer 1

intracellular signaling

Question 2

what occurs during the 3 signals of T cell activation?

Answer 2

1. Activation - pMHC:TCR (w coreceptor CD4/CD8)
2. Survival - B7:CD28 (costimulatory molecules)
3. Differentiation - release of cytokines

Question 3

what are 2 types of receptors involved in T cell activation?

Answer 3

1. receptors w intrinsic kinase activity
2. receptors w extrinsic kinase activity

Question 4

describe receptors with intrinsic kinase activity

Answer 4

signaling is initiated by dimerization and transphosphorylation by a kinase domain that is part of the receptor

Question 5

describe receptors with extrinsic kinase activity

Answer 5

signaling is initiated by recruitment of a kinase, dimerization, and transphosphorylation

Question 6

what is SH2?

Answer 6

recognizes phosphorylated tyrosine on the receptor to allow for other proteins to join

Question 7

what are the 3 proteins responsible for regulation of signaling? and their roles?

Answer 7

1. kinases –> phosphorylation
2. phosphatases –> dephosphorylation
3. ubiquitinated –> target proteins for degradation

Question 8

what are the 4 components of the TCR complex?

Answer 8

1. TCR
2. CD3
3. ITAMs
4. zeta chains

Question 9

how is signaling initiated by TCR binding? (2)

Answer 9

pMHC:TCR bind

coreceptor (CD4, CD8) binds MHC

Question 10

what happens when signaling is initiated by TCR binding?

Answer 10

Lck is recruited to cause more signaling

Question 11

what type of protein is Lck?

Answer 11

coreceptor-associated kinase

Question 12

how does Lck cause more signaling?

Answer 12

phosphorylates ITAMs

Question 13

what happens once ITAMs are phosphorylated?

Answer 13

Zap-70 kinase is phosphorylated, causing many downstream signaling molecules to be activated

Question 14

ultimately, what does Signal 1 cause?

Answer 14

• initiation of many signaling cascades in parallel, leading to transcription of many genes

Question 15

where are costimulatory ligands located? what are 2 examples?

Answer 15

on APC

CD80/B7.1 and CD86/B7.2

Question 16

where are costimulatory receptors located? what is an example?

Answer 16

on T cell

CD28

Question 17

is CD28 a positive or negative costimulatory receptor? what does this mean?

Answer 17

positive –> allows activation of T cell

Question 18

what are 2 examples of negative costimulatory receptors? what does this cause?

Answer 18

CTLA-4 and PD-1

turn off activation of T cell –> ANERGIC T cel

Question 19

what is an anergic T cell?

Answer 19

nonresponsive/non-activated T cell

Question 20

what type of molecule is CD28? (3 qualities)

Answer 20

1. transmembrane
2. glycoprotein
3. homodimer

Question 21

where and when is CD28 found?

Answer 21

found on all naive T cells at baseline

Question 22

what does CD28 bind? when?

Answer 22

binds B7.1/CD80 and B7.2/CD86 which are expressed when APCs are activated (not baseline)

Question 23

is the kinase activity for CD28 extrinsic or intrinsic?

Answer 23

extrinsic

Question 24

what are the 4 steps for CD28 signaling?

Answer 24

1. binding to B7.1/B7.2
2. phosphorylation of CD28 receptor by extrinsic kinase
3. recruitment of another kinase via SH2
4. additional signaling

Question 25

when do T cells become anergic? (2)

Answer 25

1. negative costimulatory receptors
2. APC can’t present B7.1/B7.2 due to mutation for ex.

Question 26

when do T cells stop being anergic?

Answer 26

they don’t –> they are anergic forever, even if they receive a functional APC, then die

Question 27

WHAT OCCURS WHEN pMHC BINDS TCR?

Answer 27

1. pMHC binds TCR
2. co-receptor (CD4/CD8) binds MHC
3. Lck (co-receptor associated kinase) recruits to CD
4. Lck phosphorylates ITAMs
5. Zap-70 phosphorylated
6. downstream effects