Antibody Isotypes & Subtypes

In mammals, antibodies are classified into five main classes or isotypes – IgA, IgD, IgE, IgG and IgM. They are classed according to the heavy chain they ... CloseMenu CloseFilter HomeAntibodyResourceAntibodyOverviewAntibodyIsotypes&Subtypes AntibodyIsotypes&Subtypes Inmammals,antibodiesareclassifiedintofivemainclassesorisotypes–IgA,IgD,IgE,IgGandIgM.Theyareclassedaccordingtotheheavychaintheycontain–alpha,delta,epsilon,gamma ormu respectively.Thesedifferinthesequenceandnumberofconstantdomains,hingestructureandthevalencyoftheantibody.Antibodylightchainsfallintotwoclassesinmammals,kappaandlambda,withkappalightchainsbeingthemorecommonofthetwo.Althoughthesearerelativelydissimilarinproteinsequencetheyshareasimilarstructureandfunction. Figure.Immunoglobulinisotypes.Schematicrepresentationofthefiveimmunoglobulinclassesorisotypesinmammals. IgGisthemostabundantantibodyinnormalhumanserum,accountingfor70-85%ofthetotalimmunoglobulinpool(1).Itismonomericwithamolecularweightofapproximately150kDa,isthemajorantibodyofthesecondaryimmuneresponseandhasthelongesthalf-life(20-24days)ofthefiveimmunoglobulinclasses.IgGconsistsoffourhumansubclasses(IgG1,IgG2,IgG3andIgG4)eachcontainingadifferentheavychain.Theyarehighlyhomologousanddiffermainlyinthehingeregionandtheextenttowhichtheyactivatethehostimmunesystem.IgG1andIgG4containtwointer-chaindisulphidebondsinthehingeregion,IgG2has4andIgG3has11.DetailsofthefunctionaldifferencesbetweentheIgGsub-classesinhumanwillbedescribedinthesectiononFceffectorfunction.InmicetheIgGclassisdividedintofivesub-classes(IgG1,IgG2A,IgG2B,IgG2CandIgG3)andinrattherearefour(IgG1,IgG2A,IgG2B,IgG2C).Sub-classnomenclaturehasarisenindependentlyforeachspeciesandsothereisnogeneralrelationshipbetweenthesub-classesfromeachspecies. IgMaccountsfor5-10%oftheimmunoglobulinpoolandisthepredominantantibodyintheprimaryimmuneresponse(1).UnlikeIgG,IgMdoesnotcontainahingeregionbutdoescontainanadditionalconstantdomainandan18aminoacidtailpieceatthecarboxyterminus,whichcontainsacysteineandisinvolvedinmultimerisationofthemolecule.ItisclassicallyrepresentedasapentamerofthebasicfourchainstructureheldtogetherbyaJchainbutcanalsoexistinahexamericformwithouttheJchain(2)andasamonomeronthesurfaceofB-cells.SolubleIgMisinexcessof1MDaandthusduetoitssizeislargelyconfinedtotheintravascularpool. IgArepresentsapproximately5-15%oftheantibodypoolandeitherexistsasamonomeroradimer(1).IgAisthepredominantantibodyinmucoussecretionssuchassaliva,tears,milkandintestinaljuice.LikeIgM,themultimericformofIgAcontainsatailpieceatthecarboxyterminusandisheldtogetherbytheJchain.Thesecretorycomponentisa75kDapolypeptidechainsynthesisedbyepithelialcellsofthegutforlinkagetothedimericformofIgA.AsthenameimpliesthesecretorycomponentfacilitatesIgAtransportacrossepithelialcellsbutisalsoinvolvedinprotectingIgAsecretedintothelumenofthegutfromproteolyticdigestion. IgDaccountsforlessthan1%ofthetotalplasmaimmunoglobulinbutispresentinlargequantitiesonthemembraneofB-cells(1).IgDhasthesamebasicstructureasIgGbutwithanextendedhingeregionwhichisverysusceptibletoproteolyticdigestion.Theprecisefunctionofthisclassofantibodyisstillunknown. IgEisveryscarceintheserumbutisfoundonthebasophilsandmast-cellsofallindividuals(1).InasimilarmannertoIgM,IgEhastwoadditionalconstantdomainsinplaceofthehingeregion.ThisclassmayplayaroleinimmunitytoparasitesbutismorecommonlyassociatedwithtypeIimmediatehypersensitivity,whereanIgEimmuneresponseoccurstoinnocuousenvironmentalantigenssuchaspollenandpeanuts. <>   <>   References Cruse,J.M.,andLewis,R.E.(2010).Atlasofimmunology(BocaRaton,FL:CRCPress/Taylor&Francis). Collins,C.,Tsui,F.W.L.,andShulman,M.J.(2002).DifferentialactivationofhumanandguineapigcomplementbypentamericandhexamericIgM.Eur.J.Immunol.32,1802–1810.