[W7] Immunogenetics: Generation of Antibody and T-cell receptor diversity Flashcards
(29 cards)
Approximately how many antibody specificities can humans produce?
~2.5 × 10⁷
How many immunoglobulin loci are there?
Three – κ light chain, λ light chain, and heavy chain
Why can’t the 1 gene = 1 protein model explain antibody diversity?
The human genome has ~30,000 genes, not enough for millions of antibodies
What is combinatorial diversity?
Random combination of heavy and light chains to generate antibody variability
Which light chain is preferred in humans and mice?
Humans: κ (60%); Mice: κ (95%)
What is junctional diversity?
Imprecise joining of gene segments adds/removes nucleotides, increasing variability
What is isotype diversity?
Variation due to the class of the antibody (e.g., IgM, IgG)
What is allotype diversity?
Genetic variation between individuals in the constant regions
What is idiotype diversity?
Unique antigen-binding site variability of each antibody
Which gene segments encode light chains?
V (Variable), J (Joining), C (Constant)
Which segments are found only in heavy chains?
D (Diversity) segments
What is the order of gene rearrangement in Ig heavy chains?
D → J, then V → DJ
What is the functional result of gene rearrangement?
Unique variable region created for antigen recognition
Roughly how many V, D, and J segments are in the heavy chain locus?
39–51 V, 23–27 D, 6 J
How many C regions are in the heavy chain?
Multiple (one for each isotype)
What is allelic exclusion?
Only one allele of each Ig gene is expressed in a B cell, ensuring one specificity
Which chain rearranges first in B cell development?
The heavy chain
Which light chain rearranges first in mice?
Kappa (κ) light chain
How does gene rearrangement affect transcription?
Brings enhancer and promoter close together → boosts transcription ~10,000×
Which TCR chains are structurally similar to antibodies?
α (alpha) and β (beta) chains
What gene segments make up TCRs?
V, (D), J, C (D only in β chain)
Where does TCR gene rearrangement occur?
In the thymus, during T cell development
What are γδ T cells?
T cells with γ and δ chains; part of the innate-like immune response
Where are γδ T cells commonly found?
In mucosal tissues like the gut
