8 - Lymphocyte Receptor Genetics

Question 1

What are the 2 ways that allow the immune system to adapt to rapidly evolving pathogens?

Answer 1

generate a diverse repertoire of receptor molecules capable of recognizing microbial pathogens | minimize receptors that recognize/react with self-protein

Question 2

Which lymphocytes have randomly generated receptors?

Answer 2

only TCRs and BCRs

Question 3

What are the 4 different gene segments in the genome for lymphocyte receptors? Which segment is not on the light chain of the BCR?

Answer 3

variable | diversity (not on light, only on heavy) | joining | constant

Question 4

What are the 2 genes that control the diversity of the antibody?

Answer 4

the genes for the light and heavy portions of the B-cell receptors

Question 5

In which cells do recombination do NOT occur?

Answer 5

germ cells

Question 6

When and where does the recombination event happen?

Answer 6

in the BM or the thymus before the B-cell or T-cell leaves these tissues

Question 7

How many chains does the BCR have?

Answer 7

2 heavy | 2 light

Question 8

In which segment of the BCR does it react with an antigen and where diversity is created?

Answer 8

variable region

Question 9

What events occur during genetic recombination of the light chain of the BCR?

Answer 9

combine V to J &raquo_space;> VJ combine with C

Question 10

In which genetic recombination event is part of why there is an enormous diversity within BCRs?

Answer 10

due to the VDJ segment recombination

Question 11

What are the 4 enzymes that play a significant role in V(D)J recombination?

Answer 11

RAG1/2 | TdT | Artemis | ATM

Question 12

What is/are RAG1/2? What is it’s function? What gene segment does the RAG1/2 recognize?

Answer 12

recombinase complex | RAG1 = DNA cleavage | RAG2 = epigenetic targeting, recognizes RSS

Question 13

How will a defect in the RAG1/2 enzyme affect an individual?

Answer 13

person will not be able to get B-cells and T-cells produced = no adaptive immune response &raquo_space;> Severe combined immuno-deficiency (SCID = Bubble Boy)

Question 14

What is TdT? What is it’s function?

Answer 14

adds nontemplated nucleotides to DNA

Question 15

What is Artemis? What is it’s function?

Answer 15

cuts hairpin loops on DNA

Question 16

What is ATM? What is it’s function?

Answer 16

kinase | blocks cell cycle until DNA has been repaird

Question 17

How are the different V, D, J, and C gene sequences selected for recombination?

Answer 17

recombination is directed by signal sequences

Question 18

What are the signal sequences that select the VDJC sequences for recombination?

Answer 18

recombination signal sequences (RSS) that borders the gene segment

Question 19

What does each recombination signal sequence have?

Answer 19

conserved nonamer and heptamer sequence

Question 20

What is in between the nonamer/heptamer of the RSSs? What is significant about this?

Answer 20

12 or a 23 bp spacer sequence

Question 21

What is the 12/23 Rule?

Answer 21

12 bp heptamer/nonamer RSS must join with a 23 bp heptamer/nonamer RSS for recombination to occur (ie: bring a 23 to a 12 or vice versa)

Question 22

When are the RSS sequences cut out? What is cut out?

Answer 22

When the V and J gene segments come together | everything within the 12/23 spacers and the 12/23 spacers itself

Question 23

What events occur during genetic recombination of the heavy chain of the BCR?

Answer 23

D recombines with J first = DJ &raquo_space;> DJ combines with V &raquo_space;> VDJ combines with C

Question 24

Which enzyme brings the VJDC gene segments together?

Answer 24

Rag1/2 recombinase

Question 25

What are the 3 cleaving options that Artmis makes and which one is more common?

Answer 25

5’ overhang | 3’ overhang (most common) | blunt end

Question 26

What are P-nucleotides? Which enzyme adds them?

Answer 26

palindrome nucleotide | polymerase

Question 27

What is P-nucleotide addition dependent on?

Answer 27

how Artemis cutes the hairpin loop

Question 28

In which situation would TdT have a role in and why?

Answer 28

when Artemis creates a blunt end instead of overhang = cannot add P-nucleotides to blunt ends

Question 29

In which orientation does gene recombination occur?

Answer 29

in order OR one segment can be flipped upside down

Question 30

Which enzyme glues the DNA pieces together?

Answer 30

DNA ligase IV

Question 31

What are the 5 ways that increase antibody diversity?

Answer 31

multiple gene segments (which segments are put together) | heavy/light chain combinational diversity | P-nucleotide and N-nucleotide addition | exonuclease trimming

Question 32

How does heavy and light chain combinational diversity increases antibody diversity?

Answer 32

variable region on light chain and on heavy chain are very different from each other = when they come together = will be different than other heavy/light chain recombinations

Question 33

What process determines whether or not BCR is IgM or IgD?

Answer 33

mRNA splicing

Question 34

What process determines whether or not IgM is membrane-bound or secreted?

Answer 34

mRNA splicing

Question 35

What are the 2 subunits of TCRs?

Answer 35

alpha and beta

Question 36

How many chains does each subunit of TCRs have?

Answer 36

only one variable chain and one constant chain

Question 37

In which cells does genetic recombination only occur?

Answer 37

gametic cells during meiosis | somatic cells = only in T and B cells, no other cells

Question 38

What is the combinational diversity in TCRs?

Answer 38

when the alpha and beta chains combine

Question 39

Which enzymes are involved in DNA repair and apoptosis?

Answer 39

TdT and ATM

Question 40

Which cells is DNA ligase IV predominantly expressed in?

Answer 40

predominantly lymphocytes

Question 41

Which enzyme is NOT expressed in other cells and only in lymphocytes?

Answer 41

RAG1/2 recombinase

Question 42

What are N-nucleotides used for? (it’s purpose)

Answer 42

when Artemis cuts too much off of the DNA sequence so TdT comes in and creates an overhang with N-nucleotides