Lecture 13

Question 1

What are the features of an αβ T cell?

Answer 1

• conventional one
• CD4+/CD8+
• recognize peptides on MHC
• circulate
• can expand and become memory cells

Question 2

What are the features of γδ T cells?

Answer 2

• innate-like
• recognize stress proteins
• mostly in epithelial tissues
• no clonal expansion
• no memory response but can have a rapid response

Question 3

How do HSCs commit to T cell development?

Answer 3

1. MPP + FLT3 signalling = CLP cell
2. CLP + IL-7 receptor + thymic stromal cell secretes IL-7= proliferation of thymocytes
3. thymocyte + Notch 1 ligand on thymic stromal cells = T cell

Question 4

What is the “first checkpoint” of T cell development?

Answer 4

pairing of beta chain with the pTalphachain
(a pre-T cell receptor) (or gamma and delta chain pairing)

Question 5

What is a pre-T cell receptor?

Answer 5

super-dimer (two pre T cell receptors next to eachother)

Question 6

What tells the T cell that it can start alpha, gamma and delta rearrangements?

Answer 6

CD3 signalling

Question 7

Why can two delta regions be combined in somatic recombination?

Answer 7

12/23 rule

Question 8

What are the main steps of the antigen-independent phase T cell development?

Answer 8

1. The cell has received signals and committed to the CLP.
2. Migration to the thymus.
3. Notch ligand signaling and commitment to the T cell lineage.
4. Expression of transcription factors essential for T cell development.

Question 9

Which parts of the T cell recombine at the same time?

Answer 9

beta, gamma and delta all start at the same time

Question 10

After CD4 and CD8 expression begins, what is the next step?

Answer 10

pairing the beta chain with the alpha chain (or gamma with delta)

Question 11

What is the signal that cause the cell to REexpress RAG1/2 and TdT for alpha chain rearrangement?

Answer 11

pTalpha signalling (through CD3)

Question 12

If the alpha/beta chain wins the contest, does the gamma and delta chain stop recombining?

Answer 12

No, it continues after CD3 signalling continues

Question 13

What determines which MHC complex a TCR will choose (I or II) (instruction model)?

Answer 13

different signals depending on which one the TCR can better interact with commits that T cell to the lineage

Question 14

What is positive selection in T cells?

Answer 14

T cells that can bind weakly to one of the MHC proteins

Question 15

What are the three rounds of negative selection?

Answer 15

1. no recognition to MHC, or too much (eliminated by thymic cortical epithelial cells)
2. Bone marrow derived macrophages and DCs in THYMUS: scan for T cells that are more sensitive to self peptide
3. tested against AIRE for self reactivity

Question 16

What is MHC restriction?

Answer 16

requirement for the right MHC protein to present the right peptide to a specific TCR

Question 17

What is required for a stable interaction with TCR and MHC?

Answer 17

high affinity binding of CDR3s with the peptide

Question 18

Why would some cells mount a reaction to an HLA-unmatched organ transplant?

Answer 18

BCR’s somatic hypermutation of CDR1 and 2 increase diversity

Question 19

How do CLPs commit to the T cell lineage?`

Answer 19

• HSC differentiates into an MPP that expresses FLT3, FLT3 signalling results in a CLP that expresses IL-7
• *thymic stromal cells secrete IL-7 to support this^^, INTERACTION WITH NOTCH 1 activates signalling pathway that results in activation of transcription factors for T cell development

Question 19

How do CLPs commit to the T cell lineage?`

Answer 19

• HSC differentiates into an MPP that expresses FLT3, FLT3 signalling results in a CLP that expresses IL-7
• *thymic stromal cells secrete IL-7 to support this^^, INTERACTION WITH NOTCH 1 activates signalling pathway that results in activation of transcription factors for T cell development