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BIOL 2005 (40)

Antibody Diversity

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Carleton University
BIOL 2005
Elizabeth Nisbet

GENETIC BASIS OF ANTIBODY DIVERSITYConstant portion alleles are encoded on a single locusVariable regions have multiple lociStructural basis of antigen binding3D Structure of Ig DomainsAntibody sequence variability is clusteredvariability of different observed aas frequency of most commonrange1least400mostobserve clustering in 3 HYPERVARIABLE regionsinterspersed by FRAMEWORK regionstrue for light and heavy chainshypervariable regions involved in antigen bindingalso called CDRs complementarity determining regions3D structure of antibody domainsall domains have IMMUNOGLOBULIN foldall fold ind into a globular domain and there is interaction between H and LCCV interacts w VHLThree hypervariable regions brought together as three loops that extend from ends of VH and VLHypervariable regions cap the distal end3D structures of antibodyligand binding1 larger proteinsmore interaction more CDRs involved2 framework residues contact somewhat3 epitope surface of antigen that contacts Ab composed of noncontiguous AA residues3 large interacting surfaces w high STERIC complementarity4 hydrophobicshbonds are V important5 LITTLE conf change saves energyEPITOPEminimal amt of antigen needed to bind antibodyGENERATION OF VARIABLE REGION DIVERSITY BY VDJ RECOMBINATIONkappa genes are on single genetic locus but associate wdifferent VregionsV regions are encoded by multiple gene segments somatic recombinationHC and LC are coded PIECEWISE brought together by site specific recomb during Bcell differLight Chain Genes One Recombination Igk V and J separated in germline joined during lymph Diff somatic recombination DNAIntron btw Jk and Ck spliced after transcription RNA splicingIg have multiple JC Heavy Chain Genes more important for variability3 Gene Segments VDJ 2 somatic recombinations
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