Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download No Slide Title
Document related concepts
Therapeutic gene modulation wikipedia , lookup
X-inactivation wikipedia , lookup
Metagenomics wikipedia , lookup
Genetic engineering wikipedia , lookup
Human genome wikipedia , lookup
Long non-coding RNA wikipedia , lookup
Population genetics wikipedia , lookup
Essential gene wikipedia , lookup
Human genetic variation wikipedia , lookup
Gene desert wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Quantitative trait locus wikipedia , lookup
Point mutation wikipedia , lookup
Oncogenomics wikipedia , lookup
Public health genomics wikipedia , lookup
Pathogenomics wikipedia , lookup
History of genetic engineering wikipedia , lookup
Genome editing wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Gene expression programming wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Microevolution wikipedia , lookup
Designer baby wikipedia , lookup
Ridge (biology) wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Genomic imprinting wikipedia , lookup
Minimal genome wikipedia , lookup
Genome (book) wikipedia , lookup
Gene expression profiling wikipedia , lookup
Transcript
IgGs: Somatic recombination and combinatorial diversity Immune system - recognition of “self” vs. “non-self” Hallmarks of immune response – specificity – memory – Ig class switching Human IgG structure 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 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 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 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) 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
