Medical Microbiology

sameclass.Inthiswayahighlevelofsequencevariabilitywasrevealedtobe

containedwithintheN-terminaldomain(variabledomain,V),whilstsuch

variabilitywascomparablyabsentwithintheotherdomains(constantdo-

mains,C).Eachlightchainconsistsofonevariabledomain(VL)andonecon-

stantdomain(CL).Incontrast,theheavychainsareroughly 440 – 550 amino

acidsinlength,andconsistoffourtofivedomains.Again,theheavychain

variableregionismadeupofonedomain(VH),whereastheconstantregion

consistseitherofthreedomains(c,a,dchains),orfourdomains(l,echains)

(CH1,CH2,CH3,andCH4).Disulfidebondslinkthelightchainstotheheavy

chainsandtheheavychainstooneanother.Anadditionaldisulfidebond

isfoundwithineachdomain.

Thethree-dimensionalformofthemoleculeformsaletterY.Thetwo

shortarmsofthis’Y’consistoffourdomainseach(VL,CL,VH,andCH1),

andthisstructurecontainstheantigen-bindingfragments—henceitsdesig-

nationasFab(fragmentantigenbinding).TheschematicpresentedinFig.2. 3

issomewhatmisleading,sincethetwovariabledomainsofthelightand

heavychainsareinrealityintertwined.Thebindingsite—adecisivestructure

foranepitopereaction—isformedbythecombinationofvariabledomains

frombothchains.Sincethetwolightchains,andthetwoheavychains,con-

tainidenticalaminoacidsequences(thisincludesthevariabledomains),each

52 2 BasicPrinciplesofImmunology

Table2. 3 AntigenRecognitionbyBandTCells

Blymphocytes Thelpercells

(CD4+)

CytotoxicTcells

(CTL;CD8+)

Recognition

structureofB

orTcell

SurfaceIg(BCR) TCR TCR

Recognized

epitope

Conformational

epitopes(noMHC

restriction)

Linearepitopesonly

(1 0 – 15 aminoacids)+

MHCclassII

Linearepitopes(pep-

tides)(8)–9–(10)

aminoacids+MHC

classI

Antigentype Proteins/carbo-

hydrates

Peptidesonly Peptidesonly

Antigen

presentation

Notnecessary ViaMHCclassII

structures

ViaMHCclassI

structures

Effectors Antibodies

(+/–complement)

Signalsinduced

bycontact

(T/Bhelp)or

cytokines

Cytotoxicitymediat-

edbycontact(per-

forin,granzyme),or

releaseofcytokines

2

Kayser, Medical Microbiology © 2005 Thieme