Breakout #4 Flashcards
What are three fundamental factors that influence TCR and BCR-dependent activation?
1) Threshold of antigen
2) Affinity of antigen
3) Localization in the membrane
Which requires more receptors to be engaged for activation: T cells or B cells?
T cells require more
How is BCR and TCR antigen engagement threshold decrease in B and T cells?
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
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)
True
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?
TCR: 20 hrs
BCR: 3-4 hrs
What does it mean if a membrane is “engaged”?
Translocates into lipid rafts
Why does the BCR have to be translocated into the lipid rafts?
To have access to the tyrosine kinase, Lyn
Why does the TCR have to be translocated into the lipid rafts?
To access Lck and Lyn
What are lipid rafts?
Regions within membrane that have increased density of cholesterol
TCR associates with ___ chains that contain ITAM motifs while BCR associates with ___ and __, which also contain ITAM motifs
CD3; Iga and Igb
True or False: The CD3 chains containing ITAM motifs are critical for initiating signals from the TCR to the cytoplasms and, ultimately, the nucleus
True
Once both of ITAM’s tyrosines become phosphorylated, what occurs?
ITAM can bind to Sh2 domains, which further propagates signal
After TCR binds to MHC+ peptide, what does CD4 interact with?
CD4 interacts with MHC II
What does the interaction of CD4 to MHC II near the TCR induce?
Lck to phosphorylate ITAM residues on CD3 and zeta chains
What does phosphorylated ITAM recruit?
ZAP-70
What is a critical molecule in TCR signaling?
ZAP-70
True or False: ZAP-70 and PKC-theta are specific for B Cells?
False - T cells
What three TF’s are the result of ZAP-70 initiated cascade?
NF-kB; NFAT; AP-1
Which cytokine does TCR signaling produce?
IL-2
What are the two main targets for T cell related disease?
- ZAP-70
- PKC-theta
What is the role of Cyclosporin A and FK506 (Tacrolimus)
- Inhibit calcineurin activity, decrease NFAT activation
- Note: toxic side effects due to lack of specificity
- Used in transplant patients
What molecule in B cell receptor signaling acts in a homologous fashion to ZAP-70 in TCR signaling?
Syk
Common feature of B cell lymphomas?
- Constitutive activation of Syk
True or False: After BCR-induced signaling, there’s an increase in co-stimulatory factors (NF-kB, Myc, anti-apoptotic proteins, and differentiation factors)
True
BCR signaling leads to an increase in BCL-6 and BLIMP, which promote?
BCL-6 and BLIMP promote differentiation of B cell
True or False: There are B cell specific proteins used during BCR signal transduction
True
What conditions can Syk inhibitors treat?
- Leukemia/lymphomas
- Auto-immunity
- Allergies
True or False: RA can be treated with Syk Inhibitors or Tacrolimus
True
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)
True
True or False: In both TCR/BCR signaling, A Lck family member is recruited to the ITAM
False - a Syk family member
What transcription factors are activated after B and T cells activate their receptor?
- NFAT
- NF-kB
- AP-1
T-cells use ___ while B cells use Syk
ZAP-70
Both B and T signaling pathways activate ___, which leads to generation of IP3 and DAG
PLC-gamma
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
PKC
