What are thymocytes?
developing T cells within the thymus
gamma delta T cells
- maintain tissue integrity
- do not express CD4 or CD8 or CD4 co-receptors
- interact with non-classical receptors
CD4 T cells
“top of pyramid of immune cells
- helper T cells
- several subtypes
- Regulate adaptive and innate immune function
- MHC II
CD8 T cells
cytotoxic T cells
direct effector function
interact with
MHC I
Thymus structure
- site of all T cell development
- TCR development within the cortex
- selection as thymocytes move from cortex to medulla
The thymus involutes with Age
reduced T cell production T cells have long half lives -CD4 4.2 yrs -CD8 6.5 yrs T cell-mediated immunity is not grossly affected
T cell progenitors don’t commit until they reach the thymus why?
Notch 1 binds to receptors on thymic epithelium and is cleaved.
-activates transcription factors and produce IL-7
Why is Notch-1 important
T cells determine that they are in the right spot by Notch signaling, and this induces responsivity to IL-7
what are the three phases of T cell development?
double-negative
double-positive
single-positive
what occurs in the double negative T cell
the beta chain rearranges to form a functional pre-TCR and this is the first check point
what occurs in the double positive T cell?
the CD8 and CD4 are expressed while the alpha chain is rearranging and then you get a functional TCR.
-Positive and negative selection occurs as the second check point
what occurs in the single positive T cell
after the T cell passes the positive and negative selection the T cell is then selected to either be CD4 or CD8, but not both
what can occur during both double negative and double positive phases?
the T cell cell become gamma:delta
if you are going to become and alpha beta T cell what rearranges first?
the Beta chain
If gamma or delta rearrange first what happens?
the Beta and alpha are suppressed
Beta-chain production drives the production of what?
CD4 and CD8 expression to make a double positive T cell
After Beta-chain rearranges what happens?
the alpha chain rearranges to form a functional TCR
what can happen during alpha chain rearrangement?
gamma:delta can rearrange and shift to a gamma:delta T cell
Does the alpha or beta chain form the pre-T cell receptor?
beta
why do are most all T cells alpha beta and not gamma delta?
because the gamma and delta have the rearrange before the one beta chain
how many attempts does the beta chain get to rearrange?
4
2 per loci and there are 2 genes
the beta chain is equivalent to what of the immunoglobulin?
the heavy chain in terms of rearrangement
what is the order of rearrangement of the beta chain?
1st: D+J=DJ
2nd: DJ+V=DJV
T/F the Beta chain locus is organized differently than immunoglobulin chains?
true
what is the first checkpiont of T cell development?
the pre-T cell receptor
What are the components of Pre-T cell receptors?
beta chain with a surrogate alpha chain analogue
what assembles after the beta chain and the surrogate alpha chain bind as a superdimer?
the CD3 complex
why is the CD3 complex important?
- drives proliferation
- RAG function halts
- also drives of expression of CD4 and CD*
once T cells become double positive what happens?
the alpha chain rearranges
why can a gamma: delta T cell still occur during alpha rearrangement?
because the delta locus is within the alpha locus
*once alpha rearranges, gamma:delta can no longer occur
what are the components of the alpha chain that rearrange?
the V and J just like the light chain of immunoglobulins
once the alpha chain has rearrange what is expressed on the surface of T cells?
functional TCR and CD4 and CD8
what is positive selection of T cells
checks for functional TCR
what is negative selection of T cells?
no self-antigen binding
positive selection ensures what?
MHC is bound by co-receptor (CD4 and CD8)
- alpha chain rearrangement can occur
- binding turns off RAG 1/2 complex
- *second check point
Positive selection: determines CD4 or CD8 expression how?
it just depends which MHC class it binds, so if it binds MHC I first then it becomes a CD8, the opposite is also true for MHC II and becoming CD4 -binding of a particular MHC will down regulate the other CD receptor type
negative selection: prevents self-antigen binding. How?
dendritic cells and macs present self peptides
- excessively binding induces apoptosis
- prevents autoreactivity
- central tolerance
- peripheral tolerance may also occur
once a T cell has passed positive and negative selection, what are they considered?
mature naive T cells
- meaning the have not bound antigen or been activated yet
what happens to the mature naive T cell?
it is released into blood steam and enters the lymph nodes for days and the move through the lymphatic system to look for antigen.
what are the Two major stages of T cell development?
double negative and double positive
what is the process of T cell receptor?
- beta rearranges to form pre-TCR and forms superdimer to express CD3 which expressed CD4 and CD8 as well as proliferation and RAG function halts.
- alpha chain rearranges and a functional TCR and CD4 and CD8 and are called double positive
