9 T Cell Development

Question 1

name of immature t cells in the thymus?

Answer 1

thymocytes

Question 2

4 key checkpoints for production of mature Tcells

Answer 2

1. Notch Signaling
2. Rearrangement of beta then alpha T cell receptor
3. Positive and negative selection to identify functional but not self reactive T cells
4. Selection of CD4, if it doesn’t match then CD8

Question 3

What are the most critical T cell maturation markers and what can they identify?

Answer 3

CD4 and CD8

• double negative stage
• double positive stage
• single positive stage

Question 4

What surface markers of T cells can differentiate 4 distinct double negative stages?

Answer 4

CD44 and CD25

Question 5

DN1 has what markers?

Answer 5

CD44 +

Question 6

DN2 has what markers?

Answer 6

CD44+ and CD25+

Question 7

DN3 has what markers ?

Answer 7

CD44(lower amount) CD 25+

Question 8

DN4 has what markers?

Answer 8

negative for CD8 and CD4 but has a pre alpha and rearranging beta
negative for CD44 and CD25

Question 9

Where does DN1 occur?

Answer 9

medulla- 10 days lineage bias

Question 10

Where does DN2 occur?

Answer 10

Cortex- Commit to tcell, 2 days

Question 11

Where does DN3 and DN4 occur?

Answer 11

Subcapsular region- TCR express 2 days DN3 2-4 days DN4

Question 12

Where does immature double positive stage take place?

Answer 12

Cortex–repetoire selection

Question 13

What determines T or B cell fate?

Answer 13

notch 1 activation —-> Tcell

loss of notch 1 —–> Bcell

Question 14

The alphbeta TCR contains # proteins from # of genes?

Answer 14

8 proteins from 6 genes

Question 15

What types of domains does the TCR have?

Answer 15

transmembrane and a constant and variable extracellular domain

Question 16

deficiencies in TCR or CD3 subunits results in?

Answer 16

decreased surface expression

Question 17

Cd3 gamma, zeta, and epsilon subunits and the TCR { subunit transmit what types of signals?

Answer 17

intracellular

Question 18

What type of recombination forms the variable regions of TCR?

Answer 18

somatic recombination that occurs in thymus

Question 19

TCR alpha gene contains what for recombination?

Answer 19

—TCR alpha chain has multiple copies of V and J and single copy of the constant. 1 V 1 J and constant are selected for final TCR alpha gene

Question 20

TCR beta gene contains what for recombination?

Answer 20

Multiple copies of V, D and J, and 2 copies of the constant region. 1 of each is selected for final TCR beta gene

Question 21

How many TCR alphas and betas on a mature T cell?

Answer 21

single alpha and single beta gene

Question 22

TCR recombination is controlled by what?

Answer 22

recombination signal sequences spaced be 23 bp on the 3’end and 12 base pairs on the 5’end

Question 23

What 2 proteins recognize the RSS sequences and facilitate alignment?

Answer 23

Rag 1 and Rag 2- catalyze cleavage of the RSS and formation of closed hairpin loops

Question 24

What encompasses the region of DNA that will encode for a functional TCR gene?

Answer 24

coding joints

Question 25

What are the intervening DNA sequences that are removed by recombination?

Answer 25

signal joints

Question 26

What binds to the coding joint and signal joint?

Answer 26

Ku70/Ku80- the recruit several proteins to ligate and create hairpin loops etcs.

Question 27

The diversity of TCR is driven by what?

Answer 27

combinatorial diversity and junctional diversity

Question 28

random selection of VDJ regions?

Answer 28

combinatorial diversity

Question 29

random addition of P and N nucleotides?

Answer 29

junctional diversity

Question 30

why is actual TCR diversity much smaller?

Answer 30

non-productive or self reactives are eliminated

Question 31

Is TCR alpha or beta rearranged first?

Answer 31

beta during the DN3 stage- formation required for further differentiation the alpha is also required for further differentiation but it comes second during the double positive stage

Question 32

Can T cells express TCR alpha chains from both genes?

Answer 32

yes, but only one is expressed on the surface

Question 33

Which chain has an intracellular tail for mediation of intracellular signaling pathways that tests the TCR beta chain?

Answer 33

pre-TCR alpha chain- only expressed during late double negative stage and early double positive stage---induces proliferation of immature thymocytes

Question 34

The inappropriate expression of TCR alpha chain is linked to what disease?

Answer 34

immature T cell leukemia

Question 35

What is the second type of TCR?

Answer 35

gamma/delta T cells.-- replaces alpha beta TCR chain and eliminates CD3 delta chain and replaces with a second copy of the CD3 gamma chain

Question 36

What happens to the alpha chain if it rearranges through all of the V and J regions before producing a functional chain?

Answer 36

apoptosis

Question 37

What must happen due to the fact that the TCR delta gene is in the TCR alpha gene?

Answer 37

rearrangement of the TCR alpha or delta is mutually exclusive---production of both is impossible in the same cell

Question 38

Once the t cell produces a TCR alpha and beta and expresses it on a surface what takes place?

Answer 38

testing for functionality and self reactivity fail function-death by neglect fail self reactivity- negative selection ONLY 2% are positively selected!!!!!!!

Question 39

what expresses self peptides to test TCR expression?

Answer 39

medulla epithelial cells

Question 40

What is down regulated in selected double positive T cells?

Answer 40

CD8

Question 41

CD4 expressing T cells with competent signaling differentiate into? incompetent?

Answer 41

CD4, incompetent leads to CD8

Question 42

What can cause immature T cell leukemia?

Answer 42

Non appropriate expression of the pre alpha chain on T cells during differentiation.