L6/7 - Ig Variation and Diversity Flashcards
What is an allotype?
Alleles in lg loci, generally in framework regions that do not impact specificity
What is an idiotype?
Variation in variable regions, up to 10^7 specificities
How is variability different Ab molecules measured?
number of different aa at a given position / frequency of most common at that position
What is somatic diversification?
Rearrangement of lg gene segments
- Rearrangement during B cell maturation (permanently changing DNA)
- Unique genes generate unique idiotype
What is the basic composition of a gene?
- Promoter/enhancer, leader exon, exons/introns, downstream enhancer and a poly A addition signal
What are the differences between types of gene segments between light chain and heavy chain?
Light chain - V J C
Heavy - V D J C
How are λ light chain gene segments organised?
[Vλ1, Vλ2, Vλn]-[Jλ1 Cλ1…Jλ4 Cλ4]
- J1C1, J2C2 - J and C segments alternate
How are κ light chain gene segments organied?
[Vκ1, Vκ2, Vκn]-[Jκ1-5]-[Cκ]
- J segments clustered followed by a single C κ locus
How are heavy chain gene segments organised?
[VH1…Vʜn]-[Dʜ1-25]-[Jʜ1-6]-[Cμ]
- Similar to κ in that each section is segmented
Is arrangement of V (D) and J segments completely random?
- 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
What happens to the gene segments in between the rearranged regions?
Permanently lost. Things upstream and downstream aren’t but aren’t transcribed either
Why does CDR3 have the highest variability?
Normal variability of CDR1 and CDR2, but also coincides with the V-J junction adding to increased variability
How does heavy chain rearrangement differ from light chain?
D - J rearrangement occurs first, followed by V - DJ rearrangement
What corresponds to the increased variability of CDR3 in the heavy chain?
- Greater than light chain
- Coincides with V-D junction as well as D-J junction
What is the recombination signal sequence (RSS)?
Recombination signal sequence found upstream or downstream of various segments.
Heptamer-12/23-Nonamer