What is the overall steps of t cell development path (5)
- Stem cell in bone marrow differentiate into common lymphoid progenitor
- CLP enters thymus (immature t cell)
- Become mature t cells
- naive t cells enter peripheral lymphoid organs and await activation by APC
- Performs function
What happens through the double negative to single positive t cell development
- Double negative: lacks CD4 or CD8 coreceptor
- Double positive: expresses both CD4 and CD8
- Single positive: expresses either CD4 or CD8
How are T cell receptors structured
- each t cell has unique TCR
- has alpha and beta chain which each have constant and variable region
How are the variable regions of the alpha and beta chains recombined
alpha-> made of only V + J gene segments
Beta-> made of V,D and J (D+ J recombine first and then V)
What is the function of Recombination signal sequences
- V, D and J genes are flanked by RSS
made up of heptameter, 23 or 12 spacer and nonamer
What is the 12/23 rule
Gene segments flanked with an RSS that contains a 12nt spacer can only recombine with a gene flanked by a RSS with a 23 nt spacer
What chromosome is the a and b chains found on
a- on chromosome 14
b- on chromosome 7
recombination only occurs between v,d,j segments located on same chromosome
What does V(D)J recombanaze do + what enzymes does it use
Complex of enzymes including recombination activating genes (RAGS)
-joins V,D or J segements and splices out the segments not used
What is junctional diversity and what adds and subtracts NTs
VDJ recombinase leaves loops which are opened by artemis
- Random NTs added by deoxynucleotidyl transferase or subtracted by exonucleases
What is TCR cross reactivity
T cells can recognize different epitopes that are similar and react to them ( molecular mimicry)
at what stage of t cell development does VDJ recombination occur
Begins during DN stage
What is the first chain to be recombined and how is it tested
B chain rearranged first and sent to cell surface to be tested by binding to surrogate a chain (DN becomes DP if passes)
What is the 2nd chain to be recombined and what is it called if it passes checks
A chain sent to cell surface and joins b chain which converts DP to SP (positive selection)
What happens in positive selection + where
Surface of epitheal cells have MHC1/2 and depending which MHC the DP TLR binds to it will change to a SP CD4 or 8
-cortex of thymus
What is linage commitment
after DP TLR binds to a specific TLR is has to stay as a CD4 or 8 cell
What occurs in negative selection and where does it occur and what does failure result in
- medulla of thymus
- Thymic medullary APC express MHCs with self antigens and if the TCR binds to strongly the t cell will undergo apoptosis
- failure of neg selection is associated with autoimmune disease
what are t cells called when they survive positive and neg selection
considered mature
-will then travel to peripheral lymphoid organs to wait for APCs
What are gamma delta t cells and how many are there
5 % of t cells mostly in mucosal tissue
innate lymphocytes that secrete cytokines and are very limited in specificity
