1. T cell development

2. T cells T cell maturation takes place in the thymus
The T cell precursor has the potential to become any lymphoid or myeloid cell
Each circulating T cell expresses a distinct T cell receptor
Each T cell receptor (TCR) can recognise a different
T cells need to interact with MHC in order to initiate an immune response
However, must not be able to respond to self proteins

3. T cell receptor The T cell receptor is related to Immunoglobulin
Consists of an  and  chain joined together by a disulphide bond
The variable region is made up of V and J sequences as seen in Ig
The  chain gene has:
50 V gene segments
70 J gene segments
The  chain gene has:
57 V gene segments
13 J gene segments
2 D gene segments
Imprecise modes of joining add to diversity
T cell receptors can only recognise foreign peptide when it is in combination with MHC

4. T cell receptors Antigen binding site Variable region Constant region
Transmembrane region
 chain
 chain

5. Thymus anatomy

6. Hematopoietic stem cell (HSC)
Hematopoietic precursor
Migration
Marrow
Blood
T cell precursor
DN1
DN4
DN2
DN3
T cell commitment
Double positive (DP)
CD4+
CD8+
Death by neglect
Other lineages including TREG, TH17, IEL, NK1.1
Thymic cortex
Potential to become B cell, dendritic cell or NK cell
Early thymocyte development
Positive and negative selection
Single positive (SP)

7. CD4+
CD8+
Negative selection
Thymic cortex
Thymic medulla
Migration
Blood
Peripheral tissues
T helper cell
Cytotoxic T cell

8. T cell development
The T cell goes through different stages of development in the different areas of the thymus
Each stage, D1-D4 are characterised by the surface molecules
In the thymus the T cell learns to interact with MHC but not respond to self antigens
DP cells which bind to MHC I become CD8+ and lose their CD4
DP cells which bind to MHC II become CD4+ and lose the CD8
T cells then exposed to self antigens within the medulla
Cells binding too strongly are negatively selected

9. T cell maturation T cell goes through different stages of development
DP express both CD4 and CD8 TCR
Each cell has a unique TCR
TCR has two binding sites
One for MHC
One for antigen
Reactivity with MHC on stromal cells checked
T cells need to bind to be able to bind to MHC
Those that cannot bind are negatively selected and die
CD4 or CD8 TCR are chosen depending on binding to MHC
TCR exposed to self antigens
Negative selection of any T cells that bind too strongly to self antigens
CD8+ cytotoxic T cells
CD4+ T helper cells
Naive until activated by
APC (usually dendritic cells)

10. Subtypes of T cells T helper cells (CD4+) Cytotoxic T cells (CD8+)
Recognise peptides on MHC class II
Activation results in rapid division and release of cytokines
Different subtypes release different cytokines
Cytotoxic T cells (CD8+)
Recognise MHC class I
Kill cells infected with virus and tumour cells
Memory T cells
Once T cells are activated (effector T cells) and release cytokines approx. 90% die
Remaining cells are long lived memory cells
Become activated by macrophages, dendritic cells and B cells
Natural Killer T cells (not the same as NK cells)
A subset of T cells which also share NK cell characteristics
Release a range of cytokines upon activation
Suppressor T cells
A CD8 T cells which functions to close down the immune response once an invading pathogen has been destroyed