T cell development Flashcards
(11 cards)
What are the main sections of the thymus
cortex: denser, mostly immature thymocytes
medulla: less dense, primary site for negative selection
DN1 stage
germline configuration
Express CD44+ CD25-
What is CD44 and CD25
○ CD44 is an adhesion molecule important for T cell activation
○ CD25 is the IL-2 receptor alpha chain
DN2 stage
- Undergo routing to the cortex and become responsive to IL-2
- CD44+ CD25+
Beta chain of TCR starts getting rearranged: D segment joins J segment - two chances
potential for gamma-delta chains to rearrange here
DN3 stage
CD44low CD25+
pairing of beta chain with a surrogate alpha chain to form pre-TCR
pre-TCR: forms complex with CD3 and pTalpha
successful rearrangement of beta chain stops RAG-1/2 and induces cell proliferation
DN4 stage
CD44- CD25-
Rapid cell proliferation occurs
starts making CD4 and CD8
represses RAG-1/2
DP stage
- Induce expression of RAG1/2
- Able to start rearranging α chain
Express both CD4 and CD8
how many chances for alpha chain rearrangement
more than beta chains
successful pairing positive selection shuts off rearrangement and progression to maturation
positive selection
thymic cortical epithelial cells present MHC
cells that cannot bind to MHC don’t receive signals
negative selection
can occur in cortex or medulla (mostly medulla)
- Medullary epithelial cells and DCs: expression of autoimmune regulator (AIRE) facilitates negative selection
○ AIRE produces peptides from all around the body
> Are able to override restrictions that would normally stop them from expressing peptides that they don’t need for their cell
when are t cells converted into regulatory T cells
when they are on the cusp of binding too tightly
> still binds to self but its okay because its for regulation not murder
