Organization/ Expression Lymphocyte Receptor Genes Flashcards

1
Q

What do the letters in V (D) J stand for?
= gene segments

A

variable/ joining/ diversity

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2
Q

Where does V (D) J recombination occur?

A

primary organs = bone marrow/ thymus

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3
Q

Why is D in brackets V (D) J ?

A

not always present/ needed for recombination
- D only in heavy chain (not light)

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4
Q

How does V (D) J recombination occur?

A

random rearrangements

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5
Q

What is the result of V (D) J recombination?

A

novel amino acid sequences in antigen-binding regions of Igs/ TCRs

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6
Q

Why is V (D) J recombination important?

A

recognition of nearly all pathogens
- including altered self-cells

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7
Q

How do B cells create different possible antibodies in developing lymphocytes?

A

Recombination of gene segments

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8
Q

Can a B cell create different possible antibodies in a mature lymphocyte?

A

no
- only in developing lymphocyte/ not once activated

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9
Q

What segments are only used in heavy chains?

A

D

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10
Q

What variable segments are present in light chain?

A

V/J

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11
Q

What variable segments are present in heavy chain?

A

V/D/J

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12
Q

Why are different gene segment combinations important?

A

recognize different antigens

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13
Q

What is the constant region gene segment?

A

C

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14
Q

What is an immunoglobulin protein?

A

Antibody

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15
Q

What are the chains in an Ig protein?

A

2 identical heavy
2 identical light

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16
Q

What are the 2 possibilities for the 2 identical light chains on an Ig protein?

A

kappa/ lambda

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17
Q

Where is each set of gene families (kappa/ lambda/ heavy chain) encoded?

A

each on separate chromosomes

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18
Q

How do you know if you are looking at a heavy/ light chain?

A

no D= light
D= heavy

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19
Q

What do kappa light-chain genes pair?

A

V / J segments

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20
Q

What do lambda light-chain genes pair?

A

J / C segment

21
Q

What segments does heavy-chain gene organization include?

A

VH/ DH/ JH/ CH

22
Q

What is required to encode the variable region of the heavy chain of the Ig molecule?

A

recombination between 3 gene segments
- VH/ D/ JH

23
Q

How is V (D) J recombination directed?

A

by a signal sequence (RSS)

24
Q

What flanks each antibody gene segment?

A

RSSs = Recombination Signal Sequences

25
Q

What happens to the spacer when 12 bp RSS and 23 bp RSS pair?

A

spacer removed

26
Q

What is needed for recombination to occur?

A

12/23 rule

27
Q

What is the 12/23 rule?

A

12 bp RSS must pair with a 23 bp RSS

28
Q

What is a one-turn spacer?

A

12 bp RSS

29
Q

What is a two-turn spacer?

A

23 bp RSS

30
Q

What is the spacer?

A

RSS

31
Q

What gene segment is the 12 bp RSS from?

A

V cluster

32
Q

What gene segment is the 23 bp RSS from?

A

J cluster

33
Q

What chain is a 2-step process for recombination?

A

Heavy

34
Q

What enzyme joins gene segments?

A

RAG 1/2 recombinase

35
Q

What does RAG stand for?

A

Recombination Activating Gene

36
Q

What enzyme (RAG 1/2 recombinase) is needed for recombination?

A

both proteins

37
Q

What RAG recombinase protein is more important?

A

RAG1

38
Q

Why is RAG1 more important?

A

forms complex with RSS stabilized by binding RAG2

39
Q

What is the role of RAG2?

A

binding stabilizes the RSS/ RAG1 complex

40
Q

What is responsible for recognizing/ cutting DNA at the immunoglobulin-encoding region/ RSS?

A

RAG1/2 complex

41
Q

What are the 10 well-defined steps of V(D)J recombination?

first 7 = both
8-10 = only heavy chain (D)

A
  1. RAG proteins recognize/ bind to RSS
  2. Cleavage of DNA
  3. Formation of hairpin at V / J region
  4. Ligation/ removal of signal ends
  5. Hairpin cleavage
  6. Overhang extension
  7. Ligation of light-chain V / J segments
  8. Exonuclease trimming
  9. N-nucleotide addition
  10. Ligation/ repair of heavy chain
42
Q

What are the 5 mechanisms to generate antibody diversity in naive B cells?

A

Multiple gene segments
Combinatory diversity (light/ heavy chain)
Templated nucleotide addition
Exonuclease trimming
Non-templated nucleotide addition

43
Q

What ensures each B cell synthesizes only 1 heavy/ 1 light chain?

A

Allelic exclusion

44
Q

What happens to potentially autoreactive receptors in light-chains?

A

Receptor editing

45
Q

What is the result of asymmetrical cleaving of hairpin structures?

A

Templated nucleotide addition
(uneven number bp)

46
Q

What involves losing nucleotides/ changing reading frames?

A

Exonuclease trimming
(randomize to fill in)

47
Q

What involves adding random nucleotides between joints?

A

Non-templated nucleotide addition

48
Q

What is non-templated nucleotide addition mediated by?

A

TdT activity