L10- T cell development

Question 1

What is the dissociation constant and affinity of the TCR?

Answer 1

Kd= 10-5
Affinity= 1/Kd
Ligand= peptide/MHC

Relatively low affinity receptor, lacks cytoplasmic signalling domains.

Question 2

How does the TCR signal successfully?

Answer 2

It contains signalling domains such as ITAM’s to pass on the signal once the T cell has bound the peptide to its TCR.

Co receptors such as CD4 , CD3 and CD8 increase signal transduction and avidity (strength of binding).

Question 3

What is the dissociation constant and affinity of Ig?

Answer 3

After maturation
Kd= 10-10
Affinity= 1/Kd
Ligand= antigen

Question 4

What are the two types of T cells (structurally)?

Answer 4

Alpha beta T cells (alpha and beta chains) most common in adults

Gamma delta T cells (gamma and delta chains) mainly found before birth in mammals.

Question 5

What is allelic exclusion?

Answer 5

Beta chain of the T cell receptor is made first and must pair with a functioning alpha chain otherwise it will die.
If the beta chain pairs with a gamma/delta chain it will also die.

Question 6

What is diversification?

Answer 6

The rearrangements involved in the formation of the beta and alpha chains of the TCR allowing diversity to be generated.
This allows the TCR to be flexible and variable to recognise the large range of different peptide antigens.

Question 7

How does the thymus develop in embryogenesis?

Answer 7

The ectoderm surrounds the endoderm and forms the thymic anlage.
This happens twice as the thymus is a bilobed structure.
The outer region is the cortex (from ectoderm) and the inner is the medulla (from endoderm).

Question 8

What are the major stages in T cell development?

Answer 8

Haematopoietic stem cells differentiate into a common lymphoid progenitor.
CLP interacts with thymic stromal cells causing them to commit to the T cell lineage.
Thymocytes develop into a double negative T cell with either alpha/beta or delta/gamma chains.
The DN T cell then develops into a double positive T cell with both CD8 and CD4 receptors.
It then develops into either a CD8 or CD4 T cell.

Question 9

What do CD44 and CD25 do?

Answer 9

CD44: An adhesion molecule that helps to hone thymocytes to the thymus.

CD25: Alpha chain of the IL2 receptor increases proliferation of T cells.

Question 10

How does positive and negative selection of T cells occur?

Answer 10

1. None or weak recognition of self peptide leads to death by neglect. (Kd<10-3M)
2. Medium strength interaction- positive selection (Kd ABOUT 10-5)
3. Strong interaction- negative selection (cell death) (Kd>10-5)

Question 11

What is the positive and negative selection of T cells?

Answer 11

Double positive T cells generated in the cortex are selected for their TCR recognition specificity by interacting with self peptide MHC complexes.

They are presented by cortical thymic epithelial cells and dendritic cells.

Question 12

How are regulatory T cells selected for?

Answer 12

High interactions with self MHC peptides

Question 13

What determines whether a thymocyte will become a helper or cytotoxic cell?

Answer 13

Whichever MHC Class molecule the developing thymocyte first interacts with determines whether it is going to become CD4+ or CD8+

Question 14

What are the CDR3 loops?

Answer 14

The ends of the alpha/beta chain form loops known as the complimentary determining regions.
Mutations occur there which adds extra specificity and diversity to the formation of the TCR.

Question 15

What percentage of thymocytes die?

Answer 15

95%

Question 16

How do T cells still respond to foreign peptides when they have only been tested on self peptides?

Answer 16

1. The anchor residues for MHC are there so they bind to MHC molecules.
2. In peripheral tissues there is increased adhesion molecule expression on T cells/APC’s allows increased interaction and signal.
3. Co-stimulatory molecules enhance T cells signals