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