Length of the antibody heavy chain complementarity determining region 3 as a specificity-determining factor
Date
2004Abstract
Theantigenbindingsiteofanantibodyismadeupofresiduesresidinginsixhypervariableloopsof the heavyandlightchains.Inmostcasesseveraloralloftheseloopsarerequiredfortheestablishmentofthe antigen-bindingsurface.Fiveoftheseloopsdisplayalimiteddiversityinlengthandsequencewhilethethird complementaritydeterminingregion(CDR)oftheheavychainishighlydifferentbetweenantibodiesnot onlywithrespecttosequencebutalsowithrespecttolength.Itsextensivediversityisakeycomponentinthe establishmentofbindingsitesallowingfortherecognitionofessentiallyanyantigenbyhumoralimmunity. Therelative importanceof its sequencevs its lengthdiversity inthiscontext ishowever, notverywell established.Toinvestigatethismatterfurtherwehaveusedanapproachemployingcombinatorialantibody librariesandantigen-specificselectioninthesearchforCDRH3lengthandsequencediversitycompatible withagivenantigenspecificity,themajorantigenicdeterminantonthetumour-associatedantigenmucin-1. InthiswaywehavenowdefinedheavychainCDR3lengthasacriticalparameterinthecreationofan antigen-specificbindingsite.Wealsoproposethatthismayreflectadependenceofaparticularstructureof thishypervariable loop, themajorcarrierofdiversity inthebindingsite, forestablishmentofagiven specificity
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