Lecture 5- Adaptive immunity 2- Part 1

Question 1

Describe the structure of B cell receptors (BCR)?

Answer 1

Two heavy chains and two light chains- making it Y shaped

Question 2

Where are the receptors expressed on the B cells?

Answer 2

On the surface

Question 3

BCR is always associated with?

Answer 3

co-transporter -made up of alpha and beta chains

Question 4

What is the function of co-transporter?

Answer 4

Transduce the signal to the B cell once BCR engages with an antigen

Question 5

Describe the structure of T cell receptor (TCR)

Answer 5

alpha chain and a beta chain heterodimer

Question 6

Is TCR associated with a co-transporter?

Answer 6

yes- CD3

Question 7

What do both co-receptors posses and what is their function?

Answer 7

Both co-receptor possess IATM (= Immunoreceptor tyrosine-based activation motif ) which enable signal transduction to take place

Question 8

How is the diversity of B cell and T cell repertoires produced?

Answer 8

somatic recombination or V(D)J recombination

Question 9

where does the recombination take place on a B cell?

Answer 9

Immunoglobulin heavy chain- found on chromosome 14

and Kappa and lambda chain genes found on chromosome 2 and 22

Question 10

Which chains goes through the V(D)J stage of recombination on BCR?

Answer 10

heavy chain

Question 11

which recombination does the light chain go through on the BCR?

Answer 11

VJ only and not stage D

Question 12

Which chromomsone does the V(D)J recombination happen in the T cells?

Answer 12

alpha chain gene- chromosome 14

beta chain -chromosome 7

Question 13

which chain in the T cells does not contain the D segement?

Answer 13

beta chain so only goes through VJ recombination

Question 14

Why is there a need to produce even more diversity in T cells than B cells?

Answer 14

1. B cells regenerate daily- T cell numbers fixed at puberty- thymus involutes
2. B cells can produce further diversity due to somatic hyper-mutation

Question 15

How are the new gene sequence produced?

Answer 15

New sequence are produced through V(D)J recombination

Question 16

How do the light chains rearrange?

Answer 16

light chains rearrangement occurs in a single step.

Question 17

how do the heavy chains rearrange?

Answer 17

Involves 2 step process-

• DJ recombination
• VDJ rearrangement

Question 18

In which phase do the DJ recombination takes place for both B cell and T cell.

Answer 18

B cells- at Pro B phase

T cells- at pro T phase

Question 19

Where does this

DJ recombination take place in B cells?

Answer 19

in the IgH gene

Question 20

where does this DJ recombination take place on T cells?

Answer 20

Alpha chain

Question 21

What happens to this new DJ segments?

Answer 21

they recombine new DJ segments with the new V segment

Question 22

Which recombination happens to the light chain?

Answer 22

Light chain undergoes VJ recombination ONLY

Question 23

What is the final destination of these genetic codes?

Answer 23

These new pieces of genetic codes are transcribed into mRNA and translated into proteins.

Question 24

What does assembly of IgH and one of the light chain result in the formation of?

Answer 24

Membrane bound immunoglobulin (IgM) and (IgD)

Question 25

where does the rearrangement of the DNA occur?

Answer 25

Occurs between specific sites on the DNA called RECOMBINATION SIGNAL SEQUENCE (RSS)

Question 26

what does these RSS sequence contain?

Answer 26

RSS sequence contain:

-CONSERVED segment of DNA composed of a heptamer, spacer and a monomer

Question 27

how does the recombination begin-

Answer 27

by binding of RAg-1 and RAG-2 complexes to the RSS- flank coding sequence to be joined

Question 28

How is the hepatmer sequence cut and at what point?

Answer 28

RAG complex is activated-

cut one strand of double-stranded DNA at the end of heptamer sequence at 5’ end

Question 29

what happens to cut 5’ end of the heptamer?

Answer 29

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

Question 30

What is the enzyme that joins the complex (hairpins and cleaved RSS ends)

Answer 30

Ku 70 and Ku 80 and DNA dependent protein kinases

Question 31

What happens to the DNA hairpins at this stage?

Answer 31

• Cleaved at random

- Additional bases may be added by enzyme TdT (terminal deoxynucleotide transferase)

Question 32

Which enzyme is responsible for removing bases at the DNA hair pins?

Answer 32

-Exonucleases- generates imprecise end

Question 33

which enzymes are used to JOIN the ends of gene sements?

Answer 33

DNA ligase

DNA- PK