T - lymphocytes Development

 

T  lymphocytes Development 

v The bone marrow – derived precursor cells that enter the thymus are not identifiable as T cells.

v They do not have a T cell receptor and bears more of the surface molecules typical of  T cells.

v The precursor T cells mature within the thymus, where they are known as thymocytes.

 

T lymphocyte Dev`t / Thymic education

v   The T cell is defined by the presence of its receptor for antigen (T cell receptor - TCR)

v   The genetic basis – rearrangement of genes coding for variable T constant chains of the molecule.

v   TCR is expressed by CD3 – involved in antigen – specific activation.

v   2/3 of T cells express surface glycoprotein CD4 + T -  cells .they are capable of promoting an immune response

v   1/3 of T cells express CD8 + T -  cells  they down regulate immune response + kill target cells

 



 

Development of thymocytes

•       Mature T cells, TCR genes are rearranged and TCR dimer expressed, along with CD3 and accessory molecule either CD4 or CD8

•       CD4 + T cell response require presentation of peptide antigens by  self MHC class   II molecules

•       CD8 + T cell response require presentation of peptide antigen by self MHC class I molecules.

•       Only 1% of precursor cells entering the thymus leave as mature T cells   

•       T cell precursor enters the thymus and becomes recognized as a potential T lymphocyte once the rearranged genes of the β chain give rise to a cytoplasmic receptor.

•       The α chain is subsequently rearranged and expressed, and following this, the CD3 complex, and both CD4  and CD8 molecules appear on the thymocyte surface.

•       There is encounter between these immature thymocytes and peptide antigen presented in the grooves of class II and class I molecules.

•       Having both CD4 and CD8, the thymocyte can potentially interact with whichever  presenting molecule is appropriate

 

Positive selection for CD4 and CD8

     -  T cells recognize antigen peptides only when presented by self MHC molecules on APC.

       1. No. of affinity  of the rearranged TCR for peptides presented by class I or II MHC molecules leaves the cell without  positive development signal i.e. death

      2.  High affinity  for the peptide – MHC complex is dangerous – the same self peptide could be encountered in the periphery by a mature T cell – with disastrous consequences. these cells also receive – auto-immunity deletion signal

    3. 3.  Moderate affinity for peptide-class 1 MHC complex leads to positive selection signal and loss of CD4 or interaction of peptide-class II MHC complex. This  leads to positive selection of CD8 and loss of CD4

4. Moderate affinity for peptide-class 11 MHC complex leads to positive selection signal and loss of CD8 or interaction of peptide-class I MHC complex. This  leads to positive selection of CD4 and loss of CD8

Virgin t cells leaving thymus express TCR selected for binding a particular MHC -peptide complex and either CD4 or  CD8

 

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