NK and yd T cells

Question 1

Tumor that does not express MHCI on the surface and one that does are transplanted to a syngenic animal. What happens?

Answer 1

MHCI- = NK cells recognize missing self and destroy the tumor

MHCI+ = cells persist, because immune system treats the tumor as “self”

Question 2

Tumor that does not express MHCI on the surface and one that does are transplanted to an allogenic animal with different MHC. What happens?

Answer 2

MHCI- = tumor persists

MHCI+ = foreign MHC is recognized and attacked, tumor gets destroyed

Question 3

What are NK cells activated by? List.

Answer 3

missing self
microbial products
cytokines
stress signals
transformed cells

Question 4

Which cytokine is released upon NK cell recognizing of target cell?

Answer 4

IFN-y

Question 5

CD8 T cells and NK cells use the same mechanisms for killing the target cells (granzymes, perforin, FasL -> apoptosis). What is the difference between them?

Answer 5

NK cells kill without needing to be primed first

Question 6

Which cells express MHCI and which do not?

Answer 6

all cells express MHCI, except non-nucleated ones (=erythrocytes)

Question 7

Is recognition of missing self dependent only on absence of MHCI?

Answer 7

no - balance between activatory and inhibitory signals is the key

missing of self is actually missing of inhibitory signal by binding MHCI on the surface with inhibitory KIR (Ly49)

Question 8

Name 2 activatory receptors on NK cells and their ligands.

Answer 8

activatory KIR (Ly49):viral proteins

NKG2D:Rae-1

Question 9

Which structure do NK receptor ligands resemble?

Answer 9

MHCI

Question 10

Which protein is expressed on the cell surface and signals genotoxic stress?

Answer 10

Rae-1

Question 11

Describe an example of virus and immune system co-evolution.

Answer 11

mCMV

Stage 1:
virus infects cell
leads to downregulation of MHCI, upregulation of Rae-1
cell is recognized by NK cell and killed, virus cannot multiply

Stage 2:
virus causes expression of m157 (MHCI homolog)
NK cells recognize it as MHCI = inhibitory signal
do not kill the cell
virus can multiply

Stage 3 (in some mouse strains):
same as stage 2
but m157 binding leads to activatory signal, not inhibitory
cell gets killed

Question 12

Which TF specifies differentiation of common lymphoid precursor into NK cell?

Answer 12

Id2

Question 13

Why cannot we use Id2 KO mouse as a model of immune system lacking NK cells and how do we overcome this problem?

Answer 13

Id2 KO also lacks complete lymph node structures, so not only are NK cells missing, but also everything else

Solution:
irradiate adult WT mouse (immune organs already formed)
transplant bone marrow of Id2 KO mouse
cells (except NKs) can develop normally from HSC

Question 14

Which gating on FACS do we have to use to find NK cells?

Answer 14

CD3 vs IL-2Rb

NKs are CD3- and IL-2Rb+

Question 15

At which step of T cell development does a cell commit to either a:b or y:d fate?

Answer 15

double negative thymocyte

this is when the first recombination event happens

Question 16

How does commitment to either a:b or y:d T cell fate happen?

Answer 16

DN T cells rearrange their y:d and b TCR chains simultaneously

y: d TCR is expressed straight away; beta chain as preTCR
- > whatever happens first (by random chance) is the chosen fate because the cell then inhibits the alternative option

a: b = weak Erk = inhibits y:d
y: d = strong Erk signaling = inhibits a:b

also: when rearranging alpha chain after successful beta, delta locus is completely excised

Question 17

When do y:d T cells appear in the body?

Answer 17

in waves, mostly before birth

only Vy1/2/7 after

Question 18

Compare a:b to y:d T cells.

Answer 18

y:d =
have limited receptor diversity,
little if any clonal expansion,
are predominantly found in skin and mucosal tissues,
recognize distinct “antigens”, which are still not known exactly,
are not MHC restricted (recognize native Ag in unprocessed form),
rapidly respond,
very little evidence for memory

Question 19

yd T cells are found in the skin. Which process is somehow affected by their absence?

Answer 19

wound healing

Question 20

A wave of embryonic yd T cells seeds the skin epidermis in the mouse, where dendritic cells are found too. What’s the difference in their roles?

Answer 20

DCs recognize pathogen related antigens, bring them to lymph nodes, present to B and T cells

yd recognize stressed cells via Rae-1 receptor and trigger local effector response via IFN-y, lyse the cells, release IL-13 (B cell help, IgE production), DC maturation (-> priming T cells)