Development of T-Cells

Question 1

What is thymic involution?

Answer 1

• The thymus is fully developed at birth but begins to degrade by one year of age
• Replaced with fatty tissue
• Reduced production of T-cells with age

Question 2

True or false. The thymus is not required for T-cell immunity once established

Answer 2

True

Question 3

What happens to an uncommitted progenitor cell upon entering the thymus?

Answer 3

Induced to divide and differentiate upon contact with stroma

Question 4

What is the difference between double-positive (DP) vs. double-negative (DN) thymocytes?

Answer 4

• DP: Both CD4 and CD8 present
• DN: neither present

Question 5

What are thymocytes?

Answer 5

Immature T-cells

Question 6

When a thymocyte binds to thymic epithelium, it activates what transcription factor to initiate maturation?

Answer 6

Notch 1

Question 7

DN T cells give rise to what two functionally distinct lineages?

Answer 7

• alpha:beta
• gamma:delta

Question 8

Does synthesis of alpha:beta cells or gamma:delta cells occur more frequently?

Answer 8

alpha:beta

Question 9

What are the fates of gamma:delta and alpha:beta cells?

Answer 9

• alpha:beta - become pre-T cell and resume rearrangement of alpha, gamma, and delta genes
• gamma:delta - become mature and leave thymus to migrate to peripheral tissues

Question 10

Explain the process of formation of the T-cell receptor from a pre-TCR

Answer 10

• Heterodimerizes with another pre-TCR via pTα (surrogate alpha chain)
• Induces Lck activation to stop rearrangement of beta, gamma, and delta genes

Question 11

What surface signaling molecule is used as a marker for early progenitor cells?

Answer 11

• Kit
• Expression decreases during formation of the pre-TCR

Question 12

How long does Notch 1 stay activated during T-cell development?

Answer 12

Activated upon entering the thymus until the cell is differentiated into either a CD4 or CD8 cell

Question 13

When are RAG1 and RAG2 expressed during T-cell development?

Answer 13

• During rearrangement and formation of the pre-TCR
• During rearrangement and formation of the TCR

Question 14

What transcription factor can inhibit Notch?

Answer 14

Ikaros

Question 15

When is CD3 (signal transduction surface molecule) expressed during T-cell development?

Answer 15

Starts as a committed T-cell progenitor and continues through maturation

Question 16

Only ______ T-cells undergo positive and negative selection.

Answer 16

alpha:beta DP T-cells

Question 17

Only ___% of T-cells survive selection

Answer 17

2%

Question 18

Explain positive selection for TCR development

Answer 18

Receptors interact with MHC I or MCH II receptors made by that individual

Question 19

________ cells mediate positive selection in the thymic cortex and present self-peptides to CD4 cells via MHC II and CD8 cells via MHC I.

Answer 19

Cortical epithelial cells

Question 20

How long does a T-cell have to bind to MHC on cortical epithelial cells before it undergoes apoptosis or rearrangement of the alpha-chain?

Answer 20

3-4 days

Question 21

Explain negative selection in T-cell development

Answer 21

Cells that bind too tightly to MHC may be autoreactive and must be eleminated

Question 22

True or false. Mature T-cells do not live long in the blood and must be replenished constantly

Answer 22

False. Mature T-cells can circulate for years

Question 23

Of the following cell types, identify which ones express CD4 and/or CD8:

1. Uncommitted progenitors
2. DN thymocytes
3. DP thymocytes
4. Naive helper T-cells
5. Naive cytotoxic T-cells

Answer 23

1. Uncommitted progenitors - neither
2. DN thymocytes - neither
3. DP thymocytes - both
4. Naive helper T-cells - CD4
5. Naive cytotoxic T-cells - CD8

Question 24

What is the function of regulatory T cells (T_regs)

Answer 24

• Express CD25 on their surface, which bind self-antigen:MHC complexes
• Suppress proliferation of naive CD4 T cells binding the same antigen