Lecture 10 Flashcards
(21 cards)
Explain the germline theory of antibody diversity
Separate gene for each different Ig chain, antibody repertoire is largely inherited
Explain the somatic diversification theory of antibody diversity
Observed repertoire generated from limited number of inherited V region sequence that undergo changes within B cells during individual lifetime
What must occur for these encoding antigen receptors to be created?
genomic recombination
Describe the genetic organization of the V-region
encoded within single exon of antigen-receptor gene, HV regions that define antigen binding interspersed between four framework regions (FRs) to provide structural stability
How does the Light-Chain Variable Region get constructed?
variable (V) and joining (J) gene segments are separated in the germline DNA, during B cell development, one V and one J randomly selected and joined together to form VJ exon, generates diversity
What is the role of the Leader Peptide (L) for both light and heavy chains?
located upstream of V gene, L (leader) exon that encodes a short peptide that directs newly synthesized light chain into secretory pathway, once processed the L is cleaved off
How does the Constant (C) region get added to the light chain?
C of light chain is located in a downstream exon, after transcription RNA splicing removes introns between L and V / J and C, resulting in L-VJ-C mRNA that is translated into light chain
How does heavy chain gene rearrangement work?
Diversity (D) segment first joined to joining (J) segment, V added to make V-D-J exon
How does the Constant (C) region get added to the heavy chain?
C of heavy chain is located in a downstream exon, after transcription RNA splicing removes introns between L and V / J and C, resulting in L-V-D-J-C mRNA that is translated into heavy chain
What is a variable (V) gene segment?
large blocks that form most of the structure
What is a diversity (D) gene segment?
small connector blocks (only in heavy chains)
What is a joining (J) gene segment?
special bricks that attach to the constant region
Which chain type has more diversity? Why?
Heavy chains due to the extra D segment
Where is the human heavy chain Ig gene located?
chromosome 14
Where is the human Kappa (κ) light chain Ig gene located?
chromosome 2
Where is the human Lambda (λ) light chain Ig gene located?
chromosome 22
How and why do V,D, and J gene segments vary?
Genetic polymorphism, resulting in diversity in antibody repertoires
What are pseudogenes?
not all gene segments are functional, some have mutations that prevent them from encoding functional proteins
How is the diversity of the Ig repertoire generated?
- combinatorial diversity of gene segments
- junctional diversity
- combinatorial diversity of heavy and light chains
- somatic hypermutation: occurs only in B cells after the initiation of an immune response and introduces point mutations into the rearranged V-region genes
How does junctional diversity further enhance variability?
- RAG1 and RAG2 initiate V(D)J recombination by recognizing recombination signal sequences (RSS) and creating double stranded breaks
- Artemis opens the DNA hairpins at coding joints, allowing for further processing before ligation
- TdT adds random nucleotides, Artemis may remove nucleotides to create junctional diversity
- DNA ligase IV, along with XRCC4, seals breaks and completes recombination.
How are TCR genes expressed?
segments in a similar pattern to Ig gene segments, rearranged by same enzymes. takes place in the thymus.
