L14: T cell development and Central Tolerance

Question 1

T cell development

Answer 1

Bone marrow - thymus - blood lymphoid organs (lymph nodes, spleen, peyer’s patches)

Question 2

DiGeorge’s Syndrome

Answer 2

Disease where thymus is non-functional as the thymal epithelial cells do not properly develop

Question 3

Markers for T cell development in the thymus (4)

Answer 3

1. CD4 - coreceptor for TCR
2. CD8 - coreceptor for TCR
3. CD25 - IL-2 receptor alpha chain
4. CD44 - binds extracellular matrix

Question 4

Double Negative (DN)

Answer 4

Not CD4 or CD8

1. DN1: CD4- CD8- CD44+ CD25-
2. DN2: CD4- CD8- CD44+ CD25+
3. DN3: CD4- CD8- CD44- CD25+
4. DN4: CD4- CD8- CD44- CD25-

Question 5

Double Positive (DP)

Answer 5

express both CD4 and CD8 (not usually found in the periphery

Question 6

Single Positive (SP)

Answer 6

CD4+ OR CD8+

Question 7

Signal Strength

Answer 7

Determines CD4 and CD8 T cell selection. If a T cell has NO affinity for MHC in thymus, it dies by neglect. If it has a slight affinity, the cell survives (positive selection) and too much affinity (negative selection)

Question 8

Features of positive selection in the thymus

Answer 8

1. Low affinity interactions between TCR and peptide/MHC complexes result in positive selection. This ensures that the selected TCR is MHC restricted (i.e. needs to see MHC as well as peptide to be activated)
2. Positive selection occurs at the DP stage in the thymic cortex
3. Cortical epithelial cells are one of the key APC which mediate positive selection

Question 9

Positive Selection Establishment

Answer 9

1. Normal MHC class expression: Both CD8 and CD4 T cells mature
2. MHC class 2-negative mutant: Only CD8 T cells mature
3. Mutant with MHC class 2 transgene expressed in thymic epithelium: both CD8 and CD4 T cells mature
4. Mutant with MHC class 2 transgene expressed that cannot interact with CD4: only CD8 T cells mature

Question 10

Negative selection in thymus features

Answer 10

1. High affinity interactions between TCR and peptide/MHC result in negative selection - deletion of cells by apoptosis which removes autoimmunte T cells from repertoire
2. Occurs at DP to SP transition in the thymic medullla or cortico-medullary junction
3. Medullary epithelial cells, CDs and macrophages are important APCs in negative selection
4. Tissue specific antigens can be expressed on medullary epithelial cells due to Aire (autoimmune regulator) gene expression

Question 11

Negative selection establishment

Answer 11

TCR transgenic animal injected with T cells which has a high affinity for specific ligand, meaning more cells are induced to die.