TCR Flashcards
What is the purpose of the TCR
antigen recognition
How is antigen presented to the TCR
via MHC molecules on APCs
Which domains of the TCR make up the antigen recognition site
Va and Vb
How is specificity determined
Each V domain has 3 complementarity determining region loops- Cdr3 is the most variable as this interacts with antigen
How is TCR diversity generated
VDJ recombination
Va is encoded by V and J gene segment in TCRa gene and Vb is encoded by V,D and J gene segments in TCRb gene. one of each of these segments joins to form V chain.
Junctional diversity caused by imprecise joining of fragments increases diversity
Pairing of a and b chains generates combinatorial diversity
How is it ensured that only V and J segments are able to join together
a result of recombinatorial signal sequences which flank the V and J genes. These are different lengths and only 12 and 23 lengths can join together
How is junctional diversity generated
Rag recombinase binds RSS and dimerises bring V and J segments together. the middle part is excised leaving a V and J segment which each have a hairpin loop at the end. the hairpin look is cut at a random site. nucleotides can be trimmed by exonuclease or added in a non-primed manner. single strand ends are filled and coding ends are joined together. this is the site at which CDR3 is found with highest sequence variation.
At what point in T cell development is TCR diversity generated
In the thymus before education
Which other receptors are required for TCR signalling
CD3 and z form part of the TCR complex
CD4 and CD8 are coreceptors of MHC1/2 respectively
CD28 binding in combination with TCR signalling promotes T cell proliferation and differentiation although this is not needed for activation of mature cytotoxic T cells as not all normal cells produce CD28 ligands
what is the effect of CD4+ TCR binding to MHC 2 on B cells and macrophages
B cells are stimulated to produce antibodies and macrophages increase their capacity to kill bacteria
How does granule release by cytotoxic T cells cause cell death
perforin aids granzyme entry through pores in the membrane. There are 4 granzymes produced, all of which are proteolytic enzymes. B causes DNA fragmentation and mitochondrial dysfunction through activation of procaspase 3 and BID resulting in release of proapoptotic factors incl caspase 9.
what is the cause of griscelli syndrome type 2
mutations in Rab27a which disrupt granule exocytosis
what is the cause of FHL2
mutations in perforin
