Genetics Diversity and Antibody Structure Flashcards
how do human genes code for Ig?
genetic recombination in B cells
what are the structural configurations of Ig?
either lamba or kappa
what are the two regions of the peptide structural confirmation of the light chain?
variable light (VL) and constant light constant (CL)
what two regions is the VL region coded by?
V and J
what gene is the CL region coded by
C
what is unique to B cells prior to transcription?
V and J genes are cut allowing for the different exons for each gene to recombine via V(D)J recombinase then joins them back to the C region to form the final B cell DNA of the light chain
when does the synthesis of the antibody molecule of the light chains of the take place?
during development of B cell prior to B cell maturation
what are the two enzymes in the nucleus of developing B cells?
RAG-1 and RAG-2 (recombination-activating (gene))
what happens once the kappa DNA rearrangement is completed?
it undergoes transcription yielding the primary complete RNA segment containing 5’ cap, both exons and introns and polyA tail
what happens after the splicing in the nucleus to remove the introns?
mature mRNA strand is transferred to the rough ER
what happens in the rough ER and and lumen of the ER?
it is synthesized (translated) by the ribosomes into the lumen of the ER, where the signal peptide is cleaved into a protein peptide awaiting assembly with a new heavy chain
what are recombination recognition sequences?
serve as a beacons for the V(D)J recombinase to bind and cleave the V-J DNA loop
how do we know that RAG-1 and RAG-2 have a role in the cleavage step?
effects in the RAG-1 and RAG-2 genes that code for enzymes have been linked to a primary immune deficiency called severe combined immune deficiency (SCID) (both the B and T cells are absent or non-functional)
true or false: genes that code for the lambda light chain is found on the same chromosomes as the genes for the kappa light and heavy chains
false
during B cell development the synthesis of which light chain is initiated first?
kappa before lambda
what is the difference between the lambda and kappa light chains?
λ light chain is that the λ DNA germline has ~30 Vλ segments, 4λ segments and 4Cλ segments. This would suggest it has the capacity for an even larger protein peptide diversity
what are similarities of heavy and light chain peptide synthesis?
on the DNA locus, the variable and constant segments and a variable gene segment recombination event occurs prior to transcription.
what are the major differences between heavy and light chains?
the heavy chain has an additional D-diversity gene segment coding for the variable region, post- transcription alternative splicing of the primary RNA transcript occurs resulting in a μ and δ heavy chain peptide with identical antigen epitope specificity.
the C region genes are identified with greek letter of the isotypes or subisotypes, why?
to re-enforce the point that the heavy chains
define the isotype or sub-isotype of the antibody molecule
what happens when gene expression is initiated in heavy chains?
V D J segments undergo rearrangement
what is the two step process of the V D J rearrangement?
- D and J segments are joined first
- then V-segment is joined
what does transcription of heavy chain result in?
primary RNA transcript containing
the 5’cap, leader sequence, polyA tail, rearranged variable region VDJ segment, extra J segment and the 2 closest C-region genes (μ and δ).
what is the result of alternative splicing of the primary RNA transcript of heavy chain?
results in 2 separate mRNA trans with identical variable region RNA, but different constant
region RNA.
what happens when the regions are transferred to the rough ER during heavy chain peptide synthesis?
they synthesize 2 heavy peptide chains with
variable regions specific for the same antigen epitope, but one having a μ constant heavy
peptide structure and the other having a δ constant heavy peptide structure.
