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Flashcards in TCR Deck (13):
1

What is the purpose of the TCR

antigen recognition

2

How is antigen presented to the TCR

via MHC molecules on APCs

3

Which domains of the TCR make up the antigen recognition site

Va and Vb

4

How is specificity determined

Each V domain has 3 complementarity determining region loops- Cdr3 is the most variable as this interacts with antigen

5

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

6

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

7

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.

8

At what point in T cell development is TCR diversity generated

In the thymus before education

9

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

10

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

11

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.

12

what is the cause of griscelli syndrome type 2

mutations in Rab27a which disrupt granule exocytosis

13

what is the cause of FHL2

mutations in perforin