gamma delta T cells

Question 1

Which cells split off ‘earlier’ from aB T cells? yD or iNKT /MAIT cells?

Answer 1

yD cells!

Question 2

Where are the unconventional T cells localised too? And yD T cells in particular?

Answer 2

Unlike aB T cells, don’t circulate through SLOs. Instead they are found in peripheral tissues (and treat SLOs like my other tissue)

Question 3

Localisation of iNKT cells?

Answer 3

Lots in vasculature and some in the liver.

Question 4

Localisation of MAIT cells?

Answer 4

Large abundance in the liver, also largely in mucosal surfaces and (also everywhere else).

Question 5

Localisation of yD T cells?

Answer 5

In peripheral tissues, especially concentrated at epithelial sites (intra-epithelial lymphocytes) and tissues, also in SLO (spleen) and blood. and thymus.

Question 6

Are yD cells evolutionarily conserved?

Answer 6

Yes, found in all jawed vertebrates and express the two ancient cytokines IL-17 (repair and resolution) and IFN-y killing.

Question 7

In mice, what are the skin intra-epithelial lymphocytes called?

Answer 7

The dendritic epidermal T cells (DETC)

Question 8

yD T cells aren’t motile like aB cells, what does this mean?

Answer 8

They normally stay localised in the tissue.

Question 9

what rearrangement occurs in the gamma chain of TCR?

Answer 9

Just normal V-J recombination.

Question 10

What is special about the TCR delta locus?

Answer 10

it is within the TCR a locus and is normally excised out.

you can also get tow diversity regions added in to make delta chain with VDDJ recombination.

Question 11

Why is the restriction of the yD TCR repertoire especially odd?

Answer 11

Because theoretically they are the most diverse TCR and immune recepotr.

Question 12

What TCR restricition do you see in yD T cells of the skin in mouse and humans?

Answer 12

In mice, mostly Vy5 TCRs.

In human Vdelta 1 in epithelial tissues.

Question 13

What TCR restriciton of yD t cells in blood and Lymphoid tissues?

Answer 13

Vy9Vdelta2

Question 14

Are ab or yd T cells produced in thymus first in development?

Answer 14

yd T cells produced before brith and aB T cells, they are produced in waves of TCR restriction, which are localised to body surfaces.

Question 15

What stage before do yD T cell have to come from in thymus?

Answer 15

Before the double positive stage.

yD or aB lineage depends on which recetpro expressed first and low (aB) or higher (yD) signalling.

Question 16

Is there a negative selection of yD T cells?

Answer 16

no evidence found of this, Becuase they do not under rapid expansion and production of or inflammatory cytokines following activation that could be pathogenic.

Question 17

Is there positve selection of yD T cells?

Answer 17

In mice, 17. D1 antibody recognises the surface of Vy5vdelta1 heterodimer in skin.

In vy5 knockout, reduced number of yD T cells in skin. But Vy1Vdelata1 were found that were also recognised by 17.D1 antibody.
Positively selected to enter tissues?

Question 18

What are the four broad categories of protection that yD T cells have?

Answer 18

1. Unique responses to microbial infeciton
2. Immunosurveillance ‘sensing stressed/ potential tumour cells.
3. Immunoregulatory functions ‘of conventional T cells)
4. Protective in very young animals.

Question 19

What antigens do Vy9Vdelta 2 cells of the blood respond to?

Answer 19

HMBPP

Question 20

Where does HMBPP come from?

Answer 20

Comes from isoprenoid synthesis in microbes. In humans, the MVA pathway used. Whereas in microbes the MEP pathway used. HMBPP is a derivative of the microbial MEP pathway.

Question 21

How many microbes use the MEP pathway and produce HMBPP?

Answer 21

LOooads, includes TB.

Question 22

Why is it odd that yD TCR would bind the phosphoantigen HMBPP?

Answer 22

because it is very very small compared to the normal peptides that TCRs would bind.

Question 23

Evidence that yD cells have a role in immunosurveillance?

What cells under higher surveillance?

Answer 23

In tumour models, yD- deficient mice had greater incidence of tumour formation. (synergised with aB- T cell deficiency).
Shows yD t cells detect early stages of stress that could be sign of tumours, especially in epithelial cells.
carcinomas (cancer of epithelial cells) accounts for most human cancers.

Question 24

How may yD T cells recognise tumours?

Answer 24

Via NK like recpotrs that detect molecules that are upregulated in response to stress?
May include phophoantigens that stimulate the yD TCR too.

Question 25

Early indications they yD T cells protective in young?

Answer 25

Produced before aB T cells, may provide protection in between stages where IgG/IgA protection weans and aB T cell development just beginning.

Question 26

What experiments show immunoporotectinon in young mice?

Answer 26

Infection with parasite Eimeria. In adults no difference between WT and deficient yD mice.
But in young mice, mice deficient in yD T cells had increased Eimeria eggs and gut damage.

Question 27

Spontaneous inflammation was seen in FVB yD deficient mice. What suggests yD T cells regulate conventional T cells?

Answer 27

The fact that mice deficient in both yD and ab T cells didn’t show any inflammation.

Question 28

Is lupus worse in MRL.lpr mice with ydT cell deficiency?

Answer 28

Yes.

Question 29

Is there cross talk between yD T cells and conventional cells?

Answer 29

Yes, proves concept of transitional immunity and integration of responses.