What is the central dogma?
DNA → RNA → Protein
What is DNA recombination?
Exchange of DNA between regions/chromosomes
Homologous vs non-homologous recombination?
Homologous = similar sequences Non-homologous = different sequences
Key characteristics of antigen receptor diversity?
Massive diversity via DNA rearrangement → recognize many antigens
Why is antigen receptor diversity important?
Pathogens are highly diverse
Risks of receptor diversity?
Autoimmunity (self-reactivity), DNA damage/mutations
Types of receptor diversification?
Combinatorial diversity and Junctional diversity, Combinatorial pairing, and (Somatic hypermutation – later)
How are antigen receptor genes similar to normal genes?
Both use transcription + translation
Key difference between antigen receptor genes similar to normal genes?
antigen receptor requires VDJ recombination first before transcription
Which regions determine antigen binding?
Variable regions (CDRs)
Structure of antibody?
2 heavy chains + 2 light chains
Functions of variable and constant region?
Variable= antigen binding and Constant= function
Membrane vs soluble Ig?
Membrane = BCR and Soluble = antibody
Function of Igα and Igβ?
Transmits signal inside B cell
Light chain regions contain?
Variable + constant
Heavy chain regions contain?
V, D, J + constant
Leader sequence function?
Directs protein to ER for processing and secretion
What is RAG1 and 2 complex?
Enzymes for V(D)J recombination, cutting and rejoining DNA segments
What are recombination signal sequences (RSS)?
DNA sequences recognized by RAG
Components of RSS?
Heptamer + spacer (12/23) + nonamer
What is the 12
23 rule?/ Recombination only between 12 bp and 23 bp spacers
Purpose of 12
23 rule?/ Ensures correct segment joining
Combinatorial diversity?
Different V, D, J combinations generating many receptor possibilities
Junctional diversity?
Random nucleotide addition/removal creating huge variability
What is TdT (terminal deoxynucleotidyl transferase?
Adds random nucleotides
What is Artemis?
Opens DNA hairpins during recombination
What is allelic exclusion?
One receptor specificity per cell
How does allelic exclusion happen?
If one allele rearranges successfully: Stops rearrangement of the other allele which requires productive rearrangement
Why more κ than λ?
κ rearranges first → if successful, λ not used
Recombination vs splicing?
Recombination = DNA level (VDJ) while Splicing = RNA level (joins variable + constant)
How does heavy chain variable attach to heavy chain constant?
via RNA splicing
Why is constant region order important?
Determines antibody class
Role of alternative splicing?
it controls: membrane vs secreted form and early isotype expression (e.g., IgM vs IgD)
What is αβ T cells?
Most common, recognize peptide + MHC
What is γδ T cells?
Less common, recognizing non-classical antigens and innate-like
Similarities between B cell receptor and T cell rearrangement?
Both useV(D)J recombination, RAG, junctional diversity
Differences between B cell receptor and T cell rearrangement?
BCR: secreted, hypermutation, class switching while TCR: membrane only, no hypermutation
Components of TCR complex or CD3 complex?
TCR (α + β), CD3 (γ, δ, ε), and ζ chains
Function of TCR complex or CD3 complex?
TCR recognizes antigen-MHC and CD3 and transmits signaling inside cell
What creates antigen receptor diversity?
VDJ recombination + junctional diversity + pairing