Lecture 12

Question 1

What is the primary site of T-Cell development?

Answer 1

Thymus

Question 2

In the thymus, T cells develop specific T cell markers including these four types:

Answer 2

1. TCR
2. CD3
3. CD4 or CD8

Question 3

Thymocytes in the outer cortex are:

Answer 3

immature proliferating cells

Question 4

thymocytes in the inner cortex of the thymus are:

Answer 4

mature cells undergoing selection

Question 5

What are the key players in apoptosis of many of the proliferating T cells in the thymus?

Answer 5

macrophages in the thymic cortex and medulla

Question 6

What are the successive stages in thymocyte development marked by?

Answer 6

1. status of TCR genes
2. status of TCR expression
3. Changes in cell-surface molecule expression (eg: CD#, CD4 and CD8)

Question 7

What are the two distinct lineages of T cells?

Answer 7

1. gamma delta T cells
2. alpha beta T cells (develop into CD4 abd CD8)

Question 8

What are the three stages in T cell development and where do they take place?

Answer 8

1. Double-Negative (subscapular zone of cortex)
2. Double-Positive (inner cortex)
3. Single-Positive (medulla

Question 9

Why is notch signaling important?

Answer 9

• it is essential for T cell lineage commitment
• It is also required during early phases of thymocyte differentiation up to the DN3 stage

Question 10

Which molecules are involved in notch signaling?

Answer 10

thymic epithelial cells + early T cell precursors up to DN3 thymocytes

Question 11

During what stage of T cell development is notch signaling turned off, and what facilitates it turning off?

Answer 11

• beta selection
• as a consequence of pre-TCR signaling

Question 12

What are the (3) markers of the earliest T-Cell precursors?

Answer 12

1. c-KIT: receptor for stem cell growth factor
2. CD44: adhesion molecule - homing to thymus
3. CD25: alpha chain of IL2 receptors

Question 13

When does CD3 expression first appear during the stages in T-Cell development

Answer 13

Between DN2 and DN3

Question 14

What stage of Thymocyte does a small fraction of them differentiate into gamma-delta TCR?

Answer 14

DN2

Question 15

When in the T-cell development stages does beta chain locus rearrangement occur?

Answer 15

DN3

Question 16

What (3) molecules form the Pre-T cell receptor?

Answer 16

1. rearranged beta chain
2. Pre-Talpha (surrogate chain)
3. CD3

Question 17

During what stages of alpha-beta T cell development does notch signaling occur?

Answer 17

ETP (DN1) -> DN3

Question 18

During what stages of alpha-beta T cell development does CD3 singaling occur?

Answer 18

DN2 -> SP

Question 19

During what stages of alpha-beta T cell development does IL-7R signaling occur?

Answer 19

ETP (DN1) -> DN4 ; beginning again in SP

Question 20

During what stages of alpha-beta T cell development does RAG1/2 lymphoid-specific recombinase activity occur?

Answer 20

DN3 and then again from DN4 -> end of DP

Question 21

Why is the Pre-TCR important?

Answer 21

• tests for productive TCR B chain rearrangement
• signals for proliferation and maturation
• suppresses further B chain rearrangement to prevent more than one functional beta chain to be produced as the T cell continues development (allelic exclusion)
• signals for TCR alpha rearrangement
• induces development of DP stage

Question 22

What happens after beta chain rearrangement of T cells?

Answer 22

• DN3 cells progress to DN4
• CD4 and CD8 will then both be expressed and cells will be DP

Question 23

What does expression of both CD4 and CD8 during the DP phase initiate?

Answer 23

rearrangement of the alpha chain locus

Question 24

How many attempts do T cells get at B-chain rearrangement? Why?

Answer 24

• 4
• 2 clusters of D and J gene segments

Question 25

How many attempts do T cells get at alpha chain rearrangement?

Answer 25

many attempts until positive selection or death intervenes

Question 26

an aB TCR is expressed on the cell surface of a T cell if both the ____ and ____ are productively rearranged

Answer 26

alpha and beta chains

Question 27

What is the goal of positive and negative selection of T cells?

Answer 27

to recognize foreign antigen combined with self-MHC molecules

Question 28

Where does positive selection occur and why does it occur?

Answer 28

* in the thymic cortex * only allows T cells that are able to bind to self-MHC molecules in the thymus to mature * MHC RESTRICTION!!

Question 29

Where does negative selection occur and what is its purpose?

Answer 29

* occurs in cortex and medulla * removes T cells whose TCR strongly recognize self-MHC with self-antigen * die by apoptosis in thymus * SELF-TOLERANCE!!!

Question 30

What cells test DP cells for the affinity of their T-cell receptor for MHC class I or II molecules presenting antigen?

Answer 30

Cortical thymic epithelial cells (cTECs) or antigen-presenting cells (APCs)

Question 31

Single positives in the medulla that bind to MHC molecules presenting antigen on the surface of either of these two types of cells die by apoptosis during negative selection

Answer 31

medullary thymic epithelial cells (mTECs) or dendritic cells

Question 32

During positive selection, if a T cell does not bind an MHC class II molecule, what is the likely fate of the T cell?

Answer 32

It will become a CD8 T cell

Question 33

What is the role of AIRE?

Answer 33

* in negative selection * enables thymic epithelial cells to undergo promiscuous gene expression * this enables presentation of tissue-specific (tissues outside the thymus) self-antigens to ensure that developing thymocytes to encounter a more broad range of self-antigens * important in self-tolerance