T cell development 2 Flashcards
What are double negative T cells?
T cells still in development that don’t express either CD4 or CD8
When is the RAG complex first expressed?
When the progenitor cell becomes a double thymocyte
What is the signal for the cells to rearrange their t cell receptor genes?
CD2
Which chains locus is the first to rearrange?
Beta chain locus
What happens once a productive beta chain is rearranged?
The beta chain is made, and associates with pre-T alpha
What is pre-T alpha?
Resembles an alpha chain but isnt an alpha chain receptor
What is the pre-T cell receptor made up of?
A beta chain and a pre-T alpha protein
What happens once the pre-t cell receptor is assembled?
It can signal for cell to start to proliferate
When do the alpha chain genes start to rearrange?
Once the cell has begun to proliferate following formation of the pre-t cell receptor
How do T cells have the same beta chain w/ diff alpha chains?
The beta chains are rearranged first, then the cell proliferates, then the apha chains rearrange
What do t cells become after the proliferation stage?
Double positive thymocytes
What are double positive thymocytes?
They express CD4 and CD8
Timeline of RAG expression in t cells?
Active when beta chain rearranges, inactive during proliferation, active when alpha chains rearrange
What is positive selection?
Only allowing t cells that would recognise self MHC molecules to go on and proliferate, discarding others that wouldnt recognise your own MHC
What proportion of TCRs can recognise self MHC molecules?
2% at most
What happens to the t cells that have weak/no binding to the MHC molecules in the thymus?
They are lost
When do t cells commit to becoming CD4 or CD8 positive T cells?
When they are undergoing positive selection
How do t cells become CD8 t cells?
If the t cell recognises a MHCI molecule it downregulates CD4 and becomes CD8 +ve
How do t cells become CD4 t cells?
If the t cell recognises a MHCiI molecule it downregulates CD8 and becomes CD4 +ve
What is MHC restriction?
Your T cell only recognising your own MHC molecules
What is negative selection?
Dendritic cells presenting self proteins on MHCI and MHCII–> if t cells bind strongly then the t cells will undergo apoptosis
What does AIRE stand for?
Autoimmune regulator
What does AIRE allow for?
The transcription of genes that would normally be tissue specific, in the thymus
e.g. insulin
What happens to people with defective AIRE?
They suffer from autoimmune disorders bc they cant undergo -ve selection