T Cell Development + Activation

Question 1

What is the overall steps of t cell development path (5)

Answer 1

1. Stem cell in bone marrow differentiate into common lymphoid progenitor
2. CLP enters thymus (immature t cell)
3. Become mature t cells
4. naive t cells enter peripheral lymphoid organs and await activation by APC
5. Performs function

Question 2

What happens through the double negative to single positive t cell development

Answer 2

1. Double negative: lacks CD4 or CD8 coreceptor
2. Double positive: expresses both CD4 and CD8
3. Single positive: expresses either CD4 or CD8

Question 3

How are T cell receptors structured

Answer 3

• each t cell has unique TCR

- has alpha and beta chain which each have constant and variable region

Question 4

How are the variable regions of the alpha and beta chains recombined

Answer 4

alpha-> made of only V + J gene segments

Beta-> made of V,D and J (D+ J recombine first and then V)

Question 5

What is the function of Recombination signal sequences

Answer 5

• V, D and J genes are flanked by RSS

made up of heptameter, 23 or 12 spacer and nonamer

Question 6

What is the 12/23 rule

Answer 6

Gene segments flanked with an RSS that contains a 12nt spacer can only recombine with a gene flanked by a RSS with a 23 nt spacer

Question 7

What chromosome is the a and b chains found on

Answer 7

a- on chromosome 14
b- on chromosome 7

recombination only occurs between v,d,j segments located on same chromosome

Question 8

What does V(D)J recombanaze do + what enzymes does it use

Answer 8

Complex of enzymes including recombination activating genes (RAGS)

-joins V,D or J segements and splices out the segments not used

Question 9

What is junctional diversity and what adds and subtracts NTs

Answer 9

VDJ recombinase leaves loops which are opened by artemis

• Random NTs added by deoxynucleotidyl transferase or subtracted by exonucleases

Question 10

What is TCR cross reactivity

Answer 10

T cells can recognize different epitopes that are similar and react to them ( molecular mimicry)

Question 11

at what stage of t cell development does VDJ recombination occur

Answer 11

Begins during DN stage

Question 12

What is the first chain to be recombined and how is it tested

Answer 12

B chain rearranged first and sent to cell surface to be tested by binding to surrogate a chain (DN becomes DP if passes)

Question 13

What is the 2nd chain to be recombined and what is it called if it passes checks

Answer 13

A chain sent to cell surface and joins b chain which converts DP to SP (positive selection)

Question 14

What happens in positive selection + where

Answer 14

Surface of epitheal cells have MHC1/2 and depending which MHC the DP TLR binds to it will change to a SP CD4 or 8

-cortex of thymus

Question 15

What is linage commitment

Answer 15

after DP TLR binds to a specific TLR is has to stay as a CD4 or 8 cell

Question 16

What occurs in negative selection and where does it occur and what does failure result in

Answer 16

• medulla of thymus
• Thymic medullary APC express MHCs with self antigens and if the TCR binds to strongly the t cell will undergo apoptosis
• failure of neg selection is associated with autoimmune disease

Question 17

what are t cells called when they survive positive and neg selection

Answer 17

considered mature

-will then travel to peripheral lymphoid organs to wait for APCs

Question 18

What are gamma delta t cells and how many are there

Answer 18

5 % of t cells mostly in mucosal tissue

innate lymphocytes that secrete cytokines and are very limited in specificity