L6/7 - Ig Variation and Diversity Flashcards

1
Q

What is an allotype?

A

Alleles in lg loci, generally in framework regions that do not impact specificity

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2
Q

What is an idiotype?

A

Variation in variable regions, up to 10^7 specificities

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3
Q

How is variability different Ab molecules measured?

A

number of different aa at a given position / frequency of most common at that position

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4
Q

What is somatic diversification?

A

Rearrangement of lg gene segments

  • Rearrangement during B cell maturation (permanently changing DNA)
  • Unique genes generate unique idiotype
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5
Q

What is the basic composition of a gene?

A
  • Promoter/enhancer, leader exon, exons/introns, downstream enhancer and a poly A addition signal
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6
Q

What are the differences between types of gene segments between light chain and heavy chain?

A

Light chain - V J C

Heavy - V D J C

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7
Q

How are λ light chain gene segments organised?

A

[Vλ1, Vλ2, Vλn]-[Jλ1 Cλ1…Jλ4 Cλ4]

- J1C1, J2C2 - J and C segments alternate

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8
Q

How are κ light chain gene segments organied?

A

[Vκ1, Vκ2, Vκn]-[Jκ1-5]-[Cκ]

- J segments clustered followed by a single C κ locus

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9
Q

How are heavy chain gene segments organised?

A

[VH1…Vʜn]-[Dʜ1-25]-[Jʜ1-6]-[Cμ]

- Similar to κ in that each section is segmented

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10
Q

Is arrangement of V (D) and J segments completely random?

A
  • For the most part random, but not completely. V gene segments form rosettes bringing differently V segments to J segments with different proximity skewing randomness
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11
Q

What happens to the gene segments in between the rearranged regions?

A

Permanently lost. Things upstream and downstream aren’t but aren’t transcribed either

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12
Q

Why does CDR3 have the highest variability?

A

Normal variability of CDR1 and CDR2, but also coincides with the V-J junction adding to increased variability

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13
Q

How does heavy chain rearrangement differ from light chain?

A

D - J rearrangement occurs first, followed by V - DJ rearrangement

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14
Q

What corresponds to the increased variability of CDR3 in the heavy chain?

A
  • Greater than light chain

- Coincides with V-D junction as well as D-J junction

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15
Q

What is the recombination signal sequence (RSS)?

A

Recombination signal sequence found upstream or downstream of various segments.
Heptamer-12/23-Nonamer

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16
Q

What spacer flanks the Vʜ segment?

A

23

17
Q

What spacer flanks the Dʜ segment?

A

12

18
Q

What spacer flanks the Jʜ segment?

A

23

19
Q

How does the κ light chain differ from the λ with respect to the RSS and how do they compare to the heavy chain?

A

λ chain is similar to heavy chain in that 23 nucleotide spacer flanks the V region whereas it is inversed in the κ light chain
- 12 flanks Vκ, 23 flanks Jκ

20
Q

What is the 12/23 rule?

A

For gene segments to recombine, a spacer length of 12 matches with a spacer length of 23

21
Q

What is the role of Tdt?

A

Terminal deoxynucleotide transferase

- Inserts random non-templated encoded nucleotides between the junctions following RAG

22
Q

What is the order of switch regions and isotype genes downstream of the VDJ cassette?

A

—[[Sμ]]–Cμ(IgM)–C𝛿(IgD)–[[Sγ]]–Cγ(IgG)–[[Sε]]–Cε(IgE)—

23
Q

Is IgD/IgM selection modulated by DNA or RNA

A

RNA. Alternate splicing of mRNA

24
Q

Is transmembrane/secreted Ig modulated by DNA or RNA

A

RNA. Alternative splicing of mRNA. If read through to membrane anchor sequence, transmembrane protein added and secreted form of Ig

25
Q

What is affinity maturation?

A

Increasing affinity strength of antibodies as Ab response progresses. Through somatic hypermutation

26
Q

What is somatic hypermutation?

A

Mutations occurring predominantly in the CDR following B-cell proliferation aiming to enhance recognition of specific foreign antigen

27
Q

What is AID?

A

Activation Induced Cytidine Deaminase

  • Not mediated by RAG
  • Required for class switching
  • Converts cytosine to uridine resulting in introduction of mutations