Lecture 11

Question 1

What are the goals of T cell development

Answer 1

1. Generate functional TCRs
2. Make T cells that are self-MHC restricted (positive selection)
3. MHC specificity–> CD4 = MHC II, CD8 = MHC I
4. Eliminate T cells that are self recognizable (negative selection)

Question 2

Where does T cell development happen?

Answer 2

Develops in the thymus
-comes from common lymphoid progenitor
-T cells form in bone marrow and develop in thymus

Question 3

What is DiGeorge Syndrome?

Answer 3

Lack of thymus
-recurrent infections due to lack of T cells

Question 4

The thymus is critical for the development of?

Answer 4

Bone marrow derived T cell precursors

Question 5

What is SCID mutation?

Answer 5

Does not have the gene required for somatic recombination

Question 6

What is Nude mutation?

Answer 6

Does not have gene required for thymus formation

Question 7

Which is long lived/ self renewing, B cells or T cells?

Answer 7

T cells

Question 8

What are the important cells in the Thymus?

Answer 8

1. Thymocytes–> Developing T cells
2. Cortical epithelium cells (cTECs)
3. Medullary epithelium cells (mTECs)
4. Dendritic cells
5. Macrophages

Question 9

Which cells in thymus do not have hematopoietic origin and which origin does it have instead?

Answer 9

-Cortical epithelium cells (cTECs)
-Medullary epithelium cells (mTECs)
-Stromal cell origin

Question 10

How does CD4 and CD8 expression occur in the dot plot?

Answer 10

1. Common lymphoid progenitor starts off DOUBLE NEGATIVE has no CD4 or CD8
2. Common lymphoid lymphoid matures DOUBLE POSITIVE
3. Common lymphoid progenitor then differentiates into CD8 SINGLE POSITIVE or CD4 SINGLE POSITIVE

Question 11

Double positive is only in?

Answer 11

Thymus

Question 12

What is the first check point of T cell development

Answer 12

Functional Pre-TCR (double negative)
-Surrogate alpha chain is encoded in germline
-once Beta chain has been successfully rearranged, rearrangement of further genes stop

Question 13

What happens if the Beta chain has been successfully rearranged? What do the new receptors signal for?

Answer 13

1. Stopping TCR beta rearrangement (Allelic exclusion)–> no more RAG protein
2. Copies succesful receptors (proliferation)
3. Differentiation into next stage of development (C4 and CD8 development)

Question 14

What happens in second checkpoint of functional TCR?

Answer 14

Functional TCR (Double positive)
-Thymocyte is double positive
-Alpha chain rearrangement begins
-alpha and beta chains are brought together

Question 15

What is required for transducing both TCR and pre-TCR signaling?

Answer 15

CD3

Question 16

What is positive selection?

Answer 16

Make a T cell that is self-MHC restricted

Question 17

What does it mean to be MHC restricted?

Answer 17

T cells and its progeny will recognize specific peptide ONLY when presented by the MHC isoform/allele that positively selected it

Question 18

What happens if there is positive selection?

Answer 18

When MHC complex is recognized the thymocyte is rescued from programmed cell death–>converts to single positive

Question 19

What happens if there is no positive selection?

Answer 19

Failure to recognize MHC complex
-Apoptotic cell death due to neglect
-TCR cannot bind at all/will not be activated by dendritic cells

Question 20

During positive selection what do MHC II develop into?

Answer 20

CD4SP (SINGLE POSITIVE)

Question 21

During positive selection what do MHC I develop into?

Answer 21

CD8SP (SINGLE POSITIVE)

Question 22

What does a single positive thymocyte with normal MHC II express?

Answer 22

BOTH CD8 and CD4 mature T cells

Question 23

What does a single positive thymocyte with normal MHC II negative mutant express?

Answer 23

ONLY CD8 mature T cells

Question 24

What inhibits TCR?

Answer 24

TCR is inhibited when transgene expressed

Question 25

What does a transgenic MHC I express?

Answer 25

Single positive CD8 T cells

Question 26

What does a transgenic MHC II express?

Answer 26

Single positive CD4 T cells