Lecture 5- Adaptive immunity 2- Part 1 Flashcards
Describe the structure of B cell receptors (BCR)?
Two heavy chains and two light chains- making it Y shaped
Where are the receptors expressed on the B cells?
On the surface
BCR is always associated with?
co-transporter -made up of alpha and beta chains
What is the function of co-transporter?
Transduce the signal to the B cell once BCR engages with an antigen
Describe the structure of T cell receptor (TCR)
alpha chain and a beta chain heterodimer
Is TCR associated with a co-transporter?
yes- CD3
What do both co-receptors posses and what is their function?
Both co-receptor possess IATM (= Immunoreceptor tyrosine-based activation motif ) which enable signal transduction to take place
How is the diversity of B cell and T cell repertoires produced?
somatic recombination or V(D)J recombination
where does the recombination take place on a B cell?
Immunoglobulin heavy chain- found on chromosome 14
and Kappa and lambda chain genes found on chromosome 2 and 22
Which chains goes through the V(D)J stage of recombination on BCR?
heavy chain
which recombination does the light chain go through on the BCR?
VJ only and not stage D
Which chromomsone does the V(D)J recombination happen in the T cells?
alpha chain gene- chromosome 14
beta chain -chromosome 7
which chain in the T cells does not contain the D segement?
beta chain so only goes through VJ recombination
Why is there a need to produce even more diversity in T cells than B cells?
- B cells regenerate daily- T cell numbers fixed at puberty- thymus involutes
- B cells can produce further diversity due to somatic hyper-mutation
How are the new gene sequence produced?
New sequence are produced through V(D)J recombination
How do the light chains rearrange?
light chains rearrangement occurs in a single step.
how do the heavy chains rearrange?
Involves 2 step process-
- DJ recombination
- VDJ rearrangement
In which phase do the DJ recombination takes place for both B cell and T cell.
B cells- at Pro B phase
T cells- at pro T phase
Where does this
DJ recombination take place in B cells?
in the IgH gene
where does this DJ recombination take place on T cells?
Alpha chain
What happens to this new DJ segments?
they recombine new DJ segments with the new V segment
Which recombination happens to the light chain?
Light chain undergoes VJ recombination ONLY
What is the final destination of these genetic codes?
These new pieces of genetic codes are transcribed into mRNA and translated into proteins.
What does assembly of IgH and one of the light chain result in the formation of?
Membrane bound immunoglobulin (IgM) and (IgD)
where does the rearrangement of the DNA occur?
Occurs between specific sites on the DNA called RECOMBINATION SIGNAL SEQUENCE (RSS)
what does these RSS sequence contain?
RSS sequence contain:
-CONSERVED segment of DNA composed of a heptamer, spacer and a monomer
how does the recombination begin-
by binding of RAg-1 and RAG-2 complexes to the RSS- flank coding sequence to be joined
How is the hepatmer sequence cut and at what point?
RAG complex is activated-
cut one strand of double-stranded DNA at the end of heptamer sequence at 5’ end
what happens to cut 5’ end of the heptamer?
Reacts with the complementary uncut strand-breaking it to leave double-stranded break at the end of the heptamer sequence - FORMING A HAIRPIN by joining the cut end with complementary strand on the other side of the break
What is the enzyme that joins the complex (hairpins and cleaved RSS ends)
Ku 70 and Ku 80 and DNA dependent protein kinases
What happens to the DNA hairpins at this stage?
- Cleaved at random
- Additional bases may be added by enzyme TdT (terminal deoxynucleotide transferase)
Which enzyme is responsible for removing bases at the DNA hair pins?
-Exonucleases- generates imprecise end
which enzymes are used to JOIN the ends of gene sements?
DNA ligase
DNA- PK