L15 - T Cells - Early Lymphocyte Maturation

Question 1

What are the two distinct sets of TCR?

Answer 1

αβ and γ𝛿 TCR. Also helper, killers and more

Question 2

When and where are T cells developed?

Answer 2

In the thymus, developed fully at birth and involutes during puberty. Production occurs early in life and rapidly drops

Question 3

How do thymocytes enter the thymus?

Answer 3

Via HEV

Question 4

If the T cells do not die, what are the three principle fates?

Answer 4

• αβ T cells, further differentiation into CD4+ and CD8+ T cells
• γ𝛿 T cells. do not undergo negative and positive selection
• Invariant NKT cells

Question 5

What occurs in DN1?

Answer 5

TCR genes still in germline configuration. Cortex

Question 6

What occurs in DN2?

Answer 6

Responsive to IL-2 (CD25). β chain rearrangement commences

Question 7

What occurs in DN3/4?

Answer 7

Rearrangement continues with Vβ to DJβ; Pre-TCR testing determines whether the cell express both CD4 and CD8. Beta selection checkpoint, cells then become CD4+CD8+ and then generate proper a chains

Question 8

What happens if β chain rearrangement is successful?

Answer 8

• Pre-TCR dimerization induces proliferation. Shut dwn of RAG, induces allelic exclusion and excision of δ genes

Question 9

Can a T-cell still become a γ/δ TCR if α/β fails?

Answer 9

Yes

Question 10

What is positive selection?

Answer 10

Keeping only the thymocytes which have a T cell receptor capable of binding MHC. Upregulation of both, then downregulation of both and then only CD4+. If it receives signals again, it becomes CD4+, otherwise CD8+. Single positive

Question 11

What is negative selection?

Answer 11

Evolved to reduce autoimmunity. All thymocytes with high affinity induce apoptosis. Some cells also become regulatory T cells

Question 12

What is AIRE?

Answer 12

A transcription factor expressed in the medulla of the thymus, eliminates self-reactive T cells that would otherwise cause autoimmune disease. Exposes T cells to normal healthy proteins