B-cell survival + T-cell development and selection

A bit about the thymus:

It is divided into capsules, where epithelial cells influence T-cell development

Where do T-cells migrate to and from in the thymus?

From the cortex to the medulla

Which cells are responsible for positive selection of the immature T-cells?

Cortical epithelial cells

We start with an immature CD3^-4^-8^- thymocyte. What about cortical epithelial cells allows them to express all of the above positively?

They have MHCI and MHCII and are antigen presenting cells (APCs)

You now have double positive thymocytes. Which cell helps them become mature (one positive, one negative?) And is responsible for negative selection?

Dendritic cells! And MTEC (medullary thymic epithelial cells)

Which chain in the T-cell is rearranged first? Is homologous to the Ig heavy chain…

Beta-chain

TCR Composition

Alpha beta recognition chains

CD3 Signaling chains

Coreceptors CD4 and CD8 associate with it

What helps timing of expression of signaling molecules during T-cell development?

Signaling and adhesion events

What are the two main paths for b-chain genes?

alpha beta, or gamma delta

Do gamma delta (GD) cells have CD4 or CD8?

No.

Where would you find GD cells?

Mucosal sites and epithelial tissue

When becoming AB or GD, what happens?

Signals turn off the opposing path. They switch each other off to become the other

What allows the immature thymocytes with double negatives to become double positive?

Pre-TCR signal

The TCR alpha chain has many segments. What is the benefit of this?

Multiple chances at making productive joints

What happens to immature T-cells who bind self-peptide

Deleted. It maintains self-tolerance

What does AIRE transcription factor do?

Allow expression of tissue specific proteins.

For example, expressing ectopic tissue in the thymus increases negative selection. You expose T-cells to other bodily cells to make sure they don’t react to them.

What does T-cell(immature) fate depend on ?

Differences between positive and negative selection.

What are the 2 factors in T-cell fate (immature)?

1. Avidity of TCR

2. Differential signals → Agonist or antagonist peptides

Usually if you have the same avidity for negative and positive, they all die

T-cell fate for mature cells: Agonist peptide

Becomes antigen-presenting cell

T-cell fate for immature cells: Agonist peptide

Apoptosis (negative selection)

T-cell fate for mature cells: Antagonist peptide

T-cell inhibited

T-cell fate for immature cells: Antagonist peptide

Maturation to CD8 single positive T-cell

T-cell fate for mature cells: No recognition

T cell ignores peptide

T-cell fate for immature cells: No recognition

Apoptosis (death by neglect)