Immune receptors and signal transduction

Question 1

Name families of kinases.

Answer 1

SRC family kinases and SYK family kinases.

Question 2

What do SRC homology 2 (SH2) domains bind?

Answer 2

Phosphotyrosine

Question 3

What do SRC homology 3 (SH3) domains bind?

Answer 3

Proline rich peptides

Question 4

What do PH domains bind?

Answer 4

Phospholipids, including PIP3, a lipid moiety on the inner leaflet of the plasma membrane.

Question 5

What do tyrosine-phosphorylated ITAMs recuit?

Answer 5

SYK or ZAP70, which contain SH2 domains

Question 6

What do tyrosine-phosphorylated ITIMs recruit?

Answer 6

Tyrosine phosphotases or inositol lipid phosphotases

Question 7

Name some ITAM-containing proteins that contribute to signal transduction in immune cell receptors.

Answer 7

Zeta chain and CD3 proteins of TCR complex, Ig alpha and Ig beta of BCR complex

Question 8

What are the TCR co-receptors?

Answer 8

CD4 and CD8
They are coreceptors because they also bind MHC molecules, albeit at non-polymorphic regions.

Question 9

What does PI3-kinase phosphorylate?

Answer 9

PIP2 to generate PIP3

Question 10

Proteins containing which domain bind PIP3?

Answer 10

PH domains, such those in ITK in T cells and BTK in B cells as well as phospholipase Cy1 (PLCy1)

Question 11

What is PDK1? What does it initially bind to? What does it activate?

Answer 11

PDK1 is a serine threonine kinase. It initially binds PIP3. It is required for phosphorylation and activation of ATK, a kinase that activates mTOR.

Question 12

What are the initial steps in T cell activation that lead to phosphorylation of adaptor proteins?

Answer 12

1. CD4/CD8 and TCR bind MHC-peptide
2. LCK in CD4/CD8 phosphorylates tyrosines in ITAMs in CD3 and zeta chains
3. ZAP70 binds to phosphotyrosines in ITAMs and phosphorylates adaptor proteins, including SLP76 and LAT

Question 13

Which cytokines signal through the common gamma chain?

Answer 13

IL-2
IL-4
IL-7
IL-9
IL-15
IL-21

(2+2+3+2+6+6)

Question 14

Which kinase is used by cytokines that signal through the common gamma chain?

Answer 14

JAK3

Question 15

Name some ligands that trigger activation of NF-kB transcription factors.

Answer 15

Cytokines on the IL-1, TNF, and IL-17 families, TLR stimulation, antigen recognition

Question 16

Which domain is common to all NF-kB proteins?

Answer 16

DNA-binding REL homology domain

Question 17

Which inhibitor usually binds NF-kB?

Answer 17

IkB

Question 18

NEMO is part of which complex?

Answer 18

IkB kinase (IKK) complex

Question 19

What is the function of IKK?

Answer 19

Phosphorylates IkB, targeting it for ubiquitination and degradation, releasing NF-kB to go to the nucleus

Question 20

Which defect causes X-linked SCID?

Answer 20

Defect in common gamma chain used in receptors for IL-2, IL4, IL-7, IL-9, IL-15, and IL-21