Transcript No Slide Title

IgGs: Somatic recombination
and combinatorial diversity
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Immune system - recognition of “self”
vs. “non-self”
Hallmarks of immune response
– specificity
– memory
– Ig class switching
Human IgG structure
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2 heavy chains + 2 light chains
Constant, variable and hypervariable
regions
The conundrum: to account for ~1011
different IgG specificities - cannot be
separate gene for each (i.e., more
different antibodies than base pairs in
genome!)
The solution: combinatorial
diversity
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Mechanisms: in B cells, somatic
“rearrangement” (or recombination)
involving splicing as well as somatic
mutation
4 families of elements: V (variable), D
(diversity), J (joining) and C (constant)
– H chain: ~200 V genes, 20 D genes, 6 J
genes (plus constant region genes for each
isotype)
Antibody diversity: A
combination of mechanisms
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Combination of different V, D and J
regions
Junctional diversity in splicing these
regions together - imprecise joining with
random insertion of nucleotides
Somatic mutation within V region genes
Finally, combinations of pairing of H
chain isotypes and L-chain subtypes
(kappa and lambda)
Additional genetic mechanisms
governing Ig expression
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Isotypic exclusion: each B cell
expresses only a single H-chain isotype
and single L-chain subtype (IgM, IgG,
IgA, IgD, IgE)
Allelic exclusion: only 1 of 2 possible
alleles is expressed
Diversity of the TCR (T-cell
antigen receptor)
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TCR: a highly variable transmembrane
heterodimeric glycoprotein that plays a
role in antigen recognition
Structure is similar to Igs
Combinatorial diversity generated in
similar manner
Ig and TCR genes appear to be part of
immunoglobulin gene superfamily with
shared ancestry