8 - Lymphocyte Receptor Genetics Flashcards
What are the 2 ways that allow the immune system to adapt to rapidly evolving pathogens?
generate a diverse repertoire of receptor molecules capable of recognizing microbial pathogens | minimize receptors that recognize/react with self-protein
Which lymphocytes have randomly generated receptors?
only TCRs and BCRs
What are the 4 different gene segments in the genome for lymphocyte receptors? Which segment is not on the light chain of the BCR?
variable | diversity (not on light, only on heavy) | joining | constant
What are the 2 genes that control the diversity of the antibody?
the genes for the light and heavy portions of the B-cell receptors
In which cells do recombination do NOT occur?
germ cells
When and where does the recombination event happen?
in the BM or the thymus before the B-cell or T-cell leaves these tissues
How many chains does the BCR have?
2 heavy | 2 light
In which segment of the BCR does it react with an antigen and where diversity is created?
variable region
What events occur during genetic recombination of the light chain of the BCR?
combine V to J »_space;> VJ combine with C
In which genetic recombination event is part of why there is an enormous diversity within BCRs?
due to the VDJ segment recombination
What are the 4 enzymes that play a significant role in V(D)J recombination?
RAG1/2 | TdT | Artemis | ATM
What is/are RAG1/2? What is it’s function? What gene segment does the RAG1/2 recognize?
recombinase complex | RAG1 = DNA cleavage | RAG2 = epigenetic targeting, recognizes RSS
How will a defect in the RAG1/2 enzyme affect an individual?
person will not be able to get B-cells and T-cells produced = no adaptive immune response »_space;> Severe combined immuno-deficiency (SCID = Bubble Boy)
What is TdT? What is it’s function?
adds nontemplated nucleotides to DNA
What is Artemis? What is it’s function?
cuts hairpin loops on DNA
What is ATM? What is it’s function?
kinase | blocks cell cycle until DNA has been repaird
How are the different V, D, J, and C gene sequences selected for recombination?
recombination is directed by signal sequences
What are the signal sequences that select the VDJC sequences for recombination?
recombination signal sequences (RSS) that borders the gene segment
What does each recombination signal sequence have?
conserved nonamer and heptamer sequence
What is in between the nonamer/heptamer of the RSSs? What is significant about this?
12 or a 23 bp spacer sequence
What is the 12/23 Rule?
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)
When are the RSS sequences cut out? What is cut out?
When the V and J gene segments come together | everything within the 12/23 spacers and the 12/23 spacers itself
What events occur during genetic recombination of the heavy chain of the BCR?
D recombines with J first = DJ »_space;> DJ combines with V »_space;> VDJ combines with C
Which enzyme brings the VJDC gene segments together?
Rag1/2 recombinase
What are the 3 cleaving options that Artmis makes and which one is more common?
5’ overhang | 3’ overhang (most common) | blunt end
What are P-nucleotides? Which enzyme adds them?
palindrome nucleotide | polymerase
What is P-nucleotide addition dependent on?
how Artemis cutes the hairpin loop
In which situation would TdT have a role in and why?
when Artemis creates a blunt end instead of overhang = cannot add P-nucleotides to blunt ends
In which orientation does gene recombination occur?
in order OR one segment can be flipped upside down
Which enzyme glues the DNA pieces together?
DNA ligase IV
What are the 5 ways that increase antibody diversity?
multiple gene segments (which segments are put together) | heavy/light chain combinational diversity | P-nucleotide and N-nucleotide addition | exonuclease trimming
How does heavy and light chain combinational diversity increases antibody diversity?
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
What process determines whether or not BCR is IgM or IgD?
mRNA splicing
What process determines whether or not IgM is membrane-bound or secreted?
mRNA splicing
What are the 2 subunits of TCRs?
alpha and beta
How many chains does each subunit of TCRs have?
only one variable chain and one constant chain
In which cells does genetic recombination only occur?
gametic cells during meiosis | somatic cells = only in T and B cells, no other cells
What is the combinational diversity in TCRs?
when the alpha and beta chains combine
Which enzymes are involved in DNA repair and apoptosis?
TdT and ATM
Which cells is DNA ligase IV predominantly expressed in?
predominantly lymphocytes
Which enzyme is NOT expressed in other cells and only in lymphocytes?
RAG1/2 recombinase
What are N-nucleotides used for? (it’s purpose)
when Artemis cuts too much off of the DNA sequence so TdT comes in and creates an overhang with N-nucleotides
