Breakout #4

Question 1

What are three fundamental factors that influence TCR and BCR-dependent activation?

Answer 1

1) Threshold of antigen
2) Affinity of antigen
3) Localization in the membrane

Question 2

Which requires more receptors to be engaged for activation: T cells or B cells?

Answer 2

T cells require more

Question 3

How is BCR and TCR antigen engagement threshold decrease in B and T cells?

Answer 3

T-cells: CD28 engagement via CD80/CD86 (on APC) decreases number of TCR’s that must be engaged
B-cells: CD40 engagement by CD40L lowers BCR antigen engagement threshold

Question 4

True or False: The greater the affinity between antigen and receptor, the greater the length of time in which the receptor is engaged (and, thus, greeting signaling is achieved)

Answer 4

True

Question 5

How long must naive T cells have TCR’s engage before T cell activation occurs? How long must B cells have BCR’s engaged for until B cell activation?

Answer 5

TCR: 20 hrs
BCR: 3-4 hrs

Question 6

What does it mean if a membrane is “engaged”?

Answer 6

Translocates into lipid rafts

Question 7

Why does the BCR have to be translocated into the lipid rafts?

Answer 7

To have access to the tyrosine kinase, Lyn

Question 8

Why does the TCR have to be translocated into the lipid rafts?

Answer 8

To access Lck and Lyn

Question 9

What are lipid rafts?

Answer 9

Regions within membrane that have increased density of cholesterol

Question 10

TCR associates with ___ chains that contain ITAM motifs while BCR associates with ___ and __, which also contain ITAM motifs

Answer 10

CD3; Iga and Igb

Question 11

True or False: The CD3 chains containing ITAM motifs are critical for initiating signals from the TCR to the cytoplasms and, ultimately, the nucleus

Answer 11

True

Question 12

Once both of ITAM’s tyrosines become phosphorylated, what occurs?

Answer 12

ITAM can bind to Sh2 domains, which further propagates signal

Question 13

After TCR binds to MHC+ peptide, what does CD4 interact with?

Answer 13

CD4 interacts with MHC II

Question 14

What does the interaction of CD4 to MHC II near the TCR induce?

Answer 14

Lck to phosphorylate ITAM residues on CD3 and zeta chains

Question 15

What does phosphorylated ITAM recruit?

Answer 15

ZAP-70

Question 16

What is a critical molecule in TCR signaling?

Answer 16

ZAP-70

Question 17

True or False: ZAP-70 and PKC-theta are specific for B Cells?

Answer 17

False - T cells

Question 18

What three TF’s are the result of ZAP-70 initiated cascade?

Answer 18

NF-kB; NFAT; AP-1

Question 19

Which cytokine does TCR signaling produce?

Answer 19

IL-2

Question 20

What are the two main targets for T cell related disease?

Answer 20

• ZAP-70
• PKC-theta

Question 21

What is the role of Cyclosporin A and FK506 (Tacrolimus)

Answer 21

• Inhibit calcineurin activity, decrease NFAT activation
• Note: toxic side effects due to lack of specificity
• Used in transplant patients

Question 22

What molecule in B cell receptor signaling acts in a homologous fashion to ZAP-70 in TCR signaling?

Answer 22

Syk

Question 23

Common feature of B cell lymphomas?

Answer 23

• Constitutive activation of Syk

Question 24

True or False: After BCR-induced signaling, there’s an increase in co-stimulatory factors (NF-kB, Myc, anti-apoptotic proteins, and differentiation factors)

Answer 24

True

Question 25

BCR signaling leads to an increase in BCL-6 and BLIMP, which promote?

Answer 25

BCL-6 and BLIMP promote differentiation of B cell

Question 26

True or False: There are B cell specific proteins used during BCR signal transduction

Answer 26

True

Question 27

What conditions can Syk inhibitors treat?

Answer 27

• Leukemia/lymphomas
• Auto-immunity
• Allergies

Question 28

True or False: RA can be treated with Syk Inhibitors or Tacrolimus

Answer 28

True

Question 29

True or False: TCR and BCR are similar in that
a) the first step of both involves activation of Scr family kinases (Lck in TCR / Lyn in BCR)
b) the second step involves phosphorylation of ITAM motifs (Lck phosphorylates CD3 / Lyn phosphorylates Iga and IgB)

Answer 29

True

Question 30

True or False: In both TCR/BCR signaling, A Lck family member is recruited to the ITAM

Answer 30

False - a Syk family member

Question 31

What transcription factors are activated after B and T cells activate their receptor?

Answer 31

• NFAT
• NF-kB
• AP-1

Question 32

T-cells use ___ while B cells use Syk

Answer 32

ZAP-70

Question 33

Both B and T signaling pathways activate ___, which leads to generation of IP3 and DAG

Answer 33

PLC-gamma

Question 34

In T cells, DAG generation activates PKC-theta, which is relatively T cell specific while DAG leads to generation of other _____ isoforms in B cells

Answer 34

PKC