T Cell Development

Question 1

What is CD3?

Answer 1

Nonvariable subunits within TCR

Question 2

What is DiGeorges syndrome?

Answer 2

genetic immunodeficiency in which there is a failure to develop thymic epithelium (no T lineage cells)

Question 3

What is a nude mouse?

Answer 3

defect due to loss of transcription factor involved in thymic epithelial cell differentiation

Question 4

What is thymic involution?

Answer 4

decreased output of thymus as you get older

Question 5

Where do cells that seed the thymus come from and enter?

Answer 5

Prothymocytes from fetal liver and BM enter the thymus via blood vessels at the cortico-medullary junction

Question 6

What produces chemotactic factors that attract T cell progenitors?

Answer 6

thymic anlage/rudiment

Question 7

What controls thymocyte egress from the thymus? Where do they leave from?

Answer 7

• controlled by chemokines and sphingosine 1-phosphate receptors (lipid chemoattractant)
• leave from venules in medulla

Question 8

What is central tolerance?

Answer 8

tolerance to self-antigens that is established in the T cells developing in the central or primary lymphoid organs (thymus and BM)

Question 9

What is clonal deletion? What is it the main mechanism of? What is another name for it?

Answer 9

• elimination of immature T cells when they bind self-Ag
• central tolerance
• negative selection

Question 10

What is positive selection?

Answer 10

only T cells whose receptors can recognize ag presented by self-MHC can mature

Question 11

What rearrangments occur at DN stage?

Answer 11

TCR beta, gamma, and delta

Question 12

What stage does TCR alpha rearrangement occur at?

Answer 12

double positive

Question 13

What stage does positive and negative selection occur at?

Answer 13

double positive, after alpha rearrangment

Question 14

Which are the most mature T cells?

Answer 14

single positive cells, high levels of CD3 and TCRbeta

Question 15

What is the ratio of CD4 to CD8 cells?

Answer 15

2:1

Question 16

What are the single positive cells that have low levels of CD3 and TCR beta?

Answer 16

immature single positives, in transition between double negative and double positive

Question 17

What is the first check point in T cell development?

Answer 17

beta selection

• assesses whether TCR beta chain is functionally rearranged
• proliferates, expresses DP, terminates gamma locus, and initiates alpha locus

Question 18

Will a double positive thymocyte ever express alpha-beta, and gamma-delta?

Answer 18

No, once you rearrange one there is no reason to rearrange the other

Question 19

What is the second check point in T cell development?

Answer 19

positive and negative selection

• assesses whether TCR alpha is functionally rearranged and whether TCR is self-MHC restricted or auto-reactive
• DP goes to single positive with high TCR alpha levels

Question 20

What is death by neglect?

Answer 20

absence of interaction with DP thymocytes causes apoptosis since they need signal to survive

Question 21

If you knockout RAG, what stage are T cells stopped at?

Answer 21

double negative

Question 22

If you knockout B2 microglobulin, what cell type do you not make?

Answer 22

CD8

Question 23

What important process is mediated by AIRE?

Answer 23

-tissue-specific Ag from other parts of the body (peripheral Ag) are expressed in thymic epithelial cells in the medulla so T cells that respond to them can be destroyed

Question 24

Where does positive selection occur?

Answer 24

cortex of the thymus

Question 25

Where does negative selection occur?

Answer 25

cortex or medulla, but likely to concentrate at cortico-medullary junction and in medulla

Question 26

What cells can induce negative selection?

Answer 26

thymic dendritic cells, cortical epithelial cells, medullary epithelial cells

Question 27

What cell can’t induce negative selection? What is its function?

Answer 27

thymic macrophages, its job is to eat the apoptosed cells

Question 28

What must be upregulated to pass from cortex to the medulla?

Answer 28

TCR levels, positively selected