T cells Flashcards
where does T cell gene rearrangememt take place?
in the thymus
how do T cells move within the thymus?
T cells move from venules into the cortex, then enter the medulla prior to leaving the thymus
does negative or positive T cell selection occur first?
Positive selection occurs first and then negative selection
what are the stages of T cell progression?
Maturing T cells progress through a double negative to double positive stage to single positive stage (CD4+ or CD8+)
what supports expression of a T cell rearranged Beta chain?
Supported by an invariant pre-TCR pTalpha)
what happens if the T cell beta chain is successfully expressed?
The alpha chain then undergoes recombination
what is the order of chain rearrangment in maturing T cells?
the beta-TCR chain is arranged first and then the alpha-TCR chain
what do double positive thymocytes mature into?
CD4+ or CD8+ T cells
what confines T cell receptors?
Their ability to only recognise MHC plus peptide
What happens following thymic selection of T cells?
The T cell receptors are less variable in shape than antibody
what is a requirement of antibody?
Antibody must be able to recognise an almost infinite variety of shapes
what is CD3 comprised from?
Zeta, epsilon-gamma and epsilon-delta chains
what charge is the TCR?
T cell receptors are positively charged and so attract stuff
what mediates the association between different TCR molecules?
The charge difference in transmembrane domains
what do the TCR alpha-beta regions associate?
CD3
what are CDRs?
Complementarity Determining Regions
how many CDRs do TCRs have?
Three CDR
-CDR1
-CDR2
-CRD3
what is the role of CDR1 and CDR2 in TCR?
mainly contact MHC
what is the role of CDR3 in TCR?
Contacts mainly peptide
what encodes CDR1 and 2 in TCR?
encoded by V genes
what encodes CDR3 in TCR?
encoded by J junctions (alpha chain) of DJ junction (beta chain)
what generates diversity in the TCR gene structure?
Nucleotides are randomly added at the junctions
what is the role of iNK-T cells?
recognition of non-peptide ligands
important in cytokine secretion
- these are not natural killer cells
what is the function of alpha-beta T cells?
recognise MHC+peptides
what is the function of gamma-delta T cells?
recognise CD1 + glycolipids
what is the function of NK-T cells?
recognise CD1 + glycolipids
what is the function of MAIT cells?
recognize MR1 + Vitamin B metabolite
what are CAR T cells?
Chimeric Antigen Receptor T cells
what is the role of CAR?
to bind surface tumour antigen and activate T cell
how are CAR T cells engineered?
To express CAR comprised of tumor-binding variable antibody fragments (scFv)
scFv is fused to T cell signalling components in cytoplasm
How do T cells mediate cell death?
release of granzyme/perforin, or by cytokines destroying tumour niche
In CAR T cell response, what activates T cells?
Aggregation of cytoplasmic domains of CD28 and CD3zeta
how are CAR T cells made?
- Splice antibody Heavy and Light chain variable domains of anti-cancer antibody onto cytoplasmic domains of CD3-zeta and CD28
- transduce patients T cells with chimeric construct
-This hardwires T cells to attack the cancer
