Lecture 17 - CD8+ T cells

Question 1

What are the properties of CTL killing?

Answer 1

Rapid

Highly specific

Can serially kill many target cells

At site of infection, they do NOT need
a secondary costimulatory signal to
unleash their weapons of mass destruction

Question 2

What makes CTLs such efficient killing machines?

Answer 2

Contain preformed cytotoxic granules:

a) perforin : delivers contents of granules to target cell cytosol
b) Granzymes : serine proteases that activate apoptosis once in cytoplasm
c) Granulysins (man only) : anti-microbial activity

Question 3

Describe the co-operative CD4-APC-CD8 interaction model for CD8 T cell activation

Answer 3

CD40L-CD40 potentiates upregulation
of MHC-peptide complexes and costimulatory
molecules
4-1BB on CD8+ T cell provides survival signals
for activated CD8+ T cell when bound to its
ligand 4-1BBL on APC
IL-2 drives proliferation, IFNg drives differentiation
to the effector status- cytotoxic T cell (CTL).

Question 4

Describe how Granzyme B and Perforin mRNA expression is controlled by transcription factors
T-bet and Eomes

Answer 4

Key Points:

IFN-g produced from Th1 cell
binds IFNgR

Combined signals via the
immunological synapse and
IFNgRs trigger transcription
factor T-bet

T-bet activates transcription
of granzyme B and perforin

In absence of T-bet, transcription
factor EOMES can substitute

Question 5

Describe apoptosome formation

Answer 5

Cytochrome c complexes with Apaf-1 to form an apoptosome
Job is to recruit initiator caspase procaspase-9
Procaspase-9 is then cleaved to active caspase-9