Lecture 8: Immune Receptors and Signal Transduction I

Question 1

Activation of NF-kB pathway

Answer 1

Activated IKK phosphorylates IkB and induces poly-ubuiquination of IkB
IkB is then degraded and cytoplasmic NF-kB dimers are released and translocated to nucleus

Question 2

Adaptor protein domains

Answer 2

May contain several SH2 and SH3 domains
May have tyrosine residues for docking sites for proteins with SH2 domain
May have proline-rich sequence for binding proteins with SH3 domain

Question 3

Number of ITAMs phosphorylated represents

Answer 3

The # of phosphorylations is a cytosolic interpretation of Ag affinity to TCR
The stronger/prolonged binding of Ags to TCR results in increasing # of phosphorylated ITAMs

Question 4

Covalent addition of lipids may promote

Answer 4

Plasma membrane localization of signaling molecules

Question 5

FcyRIIB

Answer 5

Inhibitory receptor found on B cells and myeloid cells

Question 6

Strong TCR signals are required for

Answer 6

Negative selection of T cells and their death by apoptosis

Question 7

TCR complex consists of

Answer 7

alpha/beta TCR non-covalently linked to CD3 and Zeta proteins
Both a/b chains have carboxyl terminal cytoplasmic tails 5-12 AAs long
CD3 and zeta proteins serve as signal-transducing subunits

Question 8

VAV

Answer 8

Guanine nucleotide exchange factor

Question 9

No expression of LAT in a cell causes

Answer 9

Defective in TCR mediated signaling

No mature a/b T cells would be found

Question 10

SH3 domain

Answer 10

50 amino acids that bind to proline-rich stretches

Question 11

Formation of pMHC/TCR/CD4 complex provides

Answer 11

First signal through TCR associated CD3 complex to T cell

• this signal is necessary but not sufficient to stimulate naïve T cell to proliferate and differentiate
• also requires group of costimulatory molecules

Question 12

Tyr416 site on Src

Answer 12

Can be auto-phosphorylated, opening pocket and allowing substrate to gain access

Question 13

Result when TCR engagement occurs in the absence of CD80/28 co-stimulation

Answer 13

Calcium mediated signals induce the activation of NFAT only
NFAT elicits expression of Anergy inducing genes which inhibit T cell function and induce status of T cell unresponsiveness

Question 14

CD8 structure

Answer 14

Two related chains called CD8a and CD8b

• both have a single extracellular Ig domain
• both have highly basic cytoplasmic tail about 25 AAs long

Question 15

Tyr527 site on Src

Answer 15

Phosphorylation of Tyr527 inactivates Src through interaction of Tyr527 with SH2 domain, which folds Src into a close, inaccessible bundle
-dephosphorylation at this site activates it

Question 16

Ras-MAP kinases, activation of AP-1 events

Answer 16

Ag recognition- CD4/CD8 associated Lck is activated
Lck phosphorylates ITAMs of z-chain
ZAP-70 binds z-chains and self-phosphorylate to activate
ZAP-70 activates adaptor protein LAT
LAT binds GADS adaptor (Grb2) that docks GTP/GDP exchange factor SOS
SOS converts Ras-GDP to Ras GTP which activates MAP kinase and ERK
The cascade activates AP-1

Question 17

Anergy can be induced by

Answer 17

Substimulatory levels of Ags in the absence of:

• CD28:CD80 interactions between costimulatory receptors on T cells and counter receptors on APCs
• A costimulatory signal provided by soluble cytokines

Question 18

LFA-1:ICAM-1 complex and pMHC:TCR:CD4 complex and CD2:LFA3 and CD28L:CD80/86 complex

Answer 18

LFA/ICAM complex move away from MHC/TCR/CD4 complex while CD2/LFA3 and CD28/CD80/86 complexes move toward the MHC/TCR/CD4 complex

Question 19

Clonal anergy

Answer 19

Describes T cell unresponsiveness at cellular level
Hyporesponsive state characterized by reduced capacity to synthesize IL-2
Anergic T cells do not proliferate in response to Ag

Question 20

SH2 domain

Answer 20

100 amino acids that bind to phophotyrosine-containing peptides
-Present in Syk and ZAP-70 tyrosine kinases

Question 21

Which terminus of histones is modified

Answer 21

The N terminus

Question 22

Weak TCR signals are required for

Answer 22

Positive selection of T cells in the thymus

Question 23

LAT

Answer 23

Integral membrane protein that functions as adaptor

Question 24

CD4 structure

Answer 24

4 extracellular Ig-like domains

Highly basic cytoplasmic tail 38 AAs long

Question 25

SH4 domain

Answer 25

Contains myristic acid moiety, essential for its localization to the inner surface of cell membrane

Question 26

PH domain

Answer 26

Found in Tec family kinases and recognize specific phospholipids
-Btk tyrosine kinase

Question 27

Cytoplasmic tails of CD3 domain contain ____

Compare to cytoplasmic tails of TCR

Answer 27

Cytoplasmic domain of CD3 contain ITAMs, while those of the TCR do not

Question 28

GADS

Answer 28

Cytosolic adaptor protein

Question 29

Adaptor protein catalytic activity

Answer 29

They have no catalytic activity

Question 30

Immunologic synapse is imitated by

Answer 30

TCR recognition of pMHC

Question 31

SLP-76

Answer 31

Adaptor protein with proline rich domain and SH2 binding domains

Question 32

SH1 domain

Answer 32

Catalytic domain

Question 33

TCR complex contains __ signaling chains and __ ITAMs

Answer 33

6 signaling chains

10 ITAMS