length.ThegrooveofMHCclassIImoleculesisopen-ended,andcancontain
peptidesof 9 – 15 (usually 10 – 1 2)aminoacidsinlength.
Tcellscanonlyrecognizeantigenicpeptidesincombinationwitheither
MHCclassI(whichpresentsendogenouslinearpeptides,suchasthosede-
rivedfromviruses)orMHCclassII(whichpresentexogenouslinearpeptides,
suchasthosederivedfrombacterialtoxins)(Table2. 3 ).Incontrasttoanti-
bodiesthatrecognizesoluble,complex,nonlinear,three-dimensionalstruc-
tures—T-cellrecognitionisrestrictedtochangesonthesurfacesofcellssignaled
viaMHCpluspeptide.
T-cellspecificity.T-cellrecognitionthereforeinvolvestwolevelsofspecifi-
city:first,MHCpresentationmoleculesbindpeptideswithacertaindegree
ofspecificityasdeterminedbytheshapeofthegrooveandthepeptidean-
choringloci.Second,theMHC-peptidecomplexwillonlyberecognizedby
specificT-cellreceptors(TCR)onceaminimumdegreeofbindingstrength
hasbeenobtained.ForthisreasondiseasesassociatedwiththeHLAcomplex
aredeterminedlargelybythequalityofpeptidepresentation,butcanalsobe
influencedbytheavailableTCRrepertoire.
ThestructureoftheMHCgroovethereforedetermineswhich,ofallthe
potentiallyrecognizable,peptideswillactuallybepresentedasT-cellepi-
topes.Thus,thesamepeptidescannotfunctionasT-cellepitopesinallindi-
viduals.Nonetheless,certaincombinationsofpeptidesandMHCarefre-
quentlyobserved.Forexample,approximately 50 %ofCaucasianscarrythe
HLA-A2antigen,althoughthisissometimesfoundinavariantform.
Antigen-presentingcells(APC).APCsbelongtothelymphohematopoietic
system.TheyattachpeptidestoMHCclassIImoleculesforpresentationto
Tcells,andinduceT-cellresponses.Thecomplexmechanismsinvolvedin
thisprocesshavenotyetbeenfullydelineated.Stromalcellspresentin
thethymusandbonemarrow(i.e.,connectivetissuecells,dendriticcells
andnursecellsinboththymusandbonemarrow,plusepithelialcellsin
thethymus)canalsofunctionasAPCs.Thefollowingcelltypesfunction
asAPCsinperipheralsecondarylymphoidorgans:
&Circulatingmonocytes.
&Sessilemacrophagesintissues,microgliainthecentralnervoussystem.
&Bonemarrowderiveddendriticcellswithmigratorypotential—theseoc-
curascutaneousLangerhanscells,asveiledcellsduringantigentransferinto
theafferentlymphvessels,asinterdigitatingcellsinthespleenandlymph
nodes,andasinterstitialdendriticcellsorasMcellswithinMALT.
&Folliculardendriticcells(FDC)—thesearefoundwithinthegerminalcen-
tersofthesecondarylymphorgans,donotoriginateinthebonemarrow,and
donotprocessantigensbutratherbindantigen-antibodycomplexesviaFc
receptorsandcomplement(C3)receptors.62 2 BasicPrinciplesofImmunology2
Kayser, Medical Microbiology © 2005 Thieme