Immunobiology of Natural Killer Cell Receptors (Current Topics in Microbiology and Immunology)

282 Pages·2005·3.986 MB·English

by  Eric Vivier (editor), Marco Colonna (editor)

E. Vivier and M. Colonna (Eds.)
Immunobiology
of Natural
Killer Cell Receptors
With27Figuresand8Tables
123
EricVivier,DVM,PhD.
LaboratoryofNKCellsandInnateImmunity
Centred’ImmunologiedeMarseille-Luminy(CIML)
CNRS-INSERM-UniversitédelaMéditerranée
CampusdeLuminy,Case906
13288MarseilleCedex09
France
e-mail:[email protected]
MarcoColonna,M.D.
DepartmentofPathologyandImmunology
WashingtonUniversitySchoolofMedicine
WestBuilding,Rooms4724,Box8118
660SouthEuclidAve
St.Louis,MO63110
USA
e-mail:[email protected]
Coverillustration:NaturalKiller(NK)cellactivationresultsfromadynamicequilibriumbetween
complementaryandsometimeantagonistforces,suchasthatinitiatedbyactivatingreceptors
recognizing stress-induced self (e.g. NKG2D ligands) and inhibitory receptors recognizing
constitutively-expressedself(e.g.MHCclassImolecules).
LibraryofCongressCatalogNumber72-152360
ISSN 0070-217X
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ListofContents
StrategiesofNaturalKillerCellRecognitionandSignaling ................ 1
C.A.Stewart,E.Vivier,andM.Colonna
SignalTransductioninNaturalKillerCells ........................... 23
A.W.MacFarlaneIVandK.S.Campbell
TranscriptionalRegulationofNKCellReceptors ....................... 59
S.K.Anderson
ExtendingMissing-Self?FunctionalInteractionsBetweenLectin-like
Nkrp1ReceptorsonNKCellswithLectin-likeLigands................... 77
B.F.M.PlougastelandW.M.Yokoyama
TheCD2FamilyofNaturalKillerCellReceptors ....................... 91
M.E.McNerneyandV.Kumar
ImmunobiologyofHumanNKG2DandItsLigands .....................121
S.González,V.Groh,andT.Spies
NKG2Receptor-MediatedRegulationofEffectorCTLFunctions
intheHumanTissueMicroenvironment.............................139
B.JabriandB.Meresse
DendriticCell–NKCellCross-Talk:RegulationandPhysiopathology.. .......157
L.Zitvogel,M.Terme,C.Borg,andG.Trinchieri
NKCellActivatingReceptorsandTumorRecognitioninHumans ...........175
C.Bottino,L.Moretta,andA.Moretta
NKCellRecognitionofMouseCytomegalovirus-InfectedCells.............183
S.M.VidalandL.L.Lanier
NKCellReceptorsInvolvedintheResponsetoHuman
CytomegalovirusInfection ......................................207
M.Gumá,A.Angulo,andM.López-Botet
VI ListofContents
TheImpactofVariationattheKIRGeneClusteronHumanDisease .........225
M.CarringtonandM.P.Martin
NKCellsinAutoimmuneDisease..................................259
S.Johansson,H.Hall,L.Berg,andP.Höglund
SubjectIndex................................................279
ListofContributors
(Addressesstatedatthebeginningofrespectivechapters)
Anderson,S.K. 59 Lanier,L.L. 183
Angulo,A. 207 López-Botet,M. 207
MacFarlaneIV,A.W. 23
Berg,L. 259
Martin,M.P. 225
Borg,C. 157
McNerney,M.E. 91
Bottino,C. 175
Meresse,B. 139
Moretta,A. 175
Campbell,K.S. 23
Moretta,L. 175
Carrington,M. 225
Colonna,M. 1
Plougastel,B.F.M. 77
González,S. 121 Spies,T. 121
Groh,V. 121 Stewart,C.A. 1
Gumá,M. 207
Terme,M. 157
Höglund,P. 259 Trinchieri,G. 157
Hall,H. 259
Vidal,S.M. 183
Vivier,E. 1
Jabri,B. 139
Johansson,S. 259
Yokoyama,W.M. 77
Kumar,V. 91 Zitvogel,L. 157
CTMI(2006)298:1–21
(cid:1)c Springer-VerlagBerlinHeidelberg2006
StrategiesofNaturalKillerCellRecognition
andSignaling
C.A.Stewart1((cid:1))·E.Vivier1·M.Colonna2
1LabofNKCellsandInnateImmunity,Centred’ImmunologiedeMarseille-Luminy,
INSERM-CNRS-Univ.Méditerranée,CampusdeLuminy,
13288Marseillecedex09, France
[email protected]
2DepartmentofPathologyandImmunology,WashingtonUniversitySchoolof
Medicine,St.Louis,MO63110,USA
1 Introduction ........................................... 2
2 ThemesofNKCellRecognition .............................. 2
3 InhibitoryRecognitionandSignaling ......................... 3
3.1 InhibitoryReceptorsforMHCClassI .......................... 3
3.2 InhibitoryReceptorsforNon-MHCLigands ..................... 6
4 ActivatingRecognitionandSignaling ......................... 6
4.1 SomeITAM-BasedReceptors................................ 6
4.2 NKG2D ............................................... 7
4.3 ActivatingHomologsofInhibitoryMHCClassIReceptors ........... 7
5 TheNKCellActivationCascade:FromSurfaceTriggerstoEffectorFunction 8
6 ComplexitiesinNKCellActivation ........................... 10
6.1 ConsequencesofITIMPhosphorylation ........................ 10
6.2 2B4InhibitionandActivation ............................... 10
6.3 RolesofAdhesion........................................ 11
6.4 CytotoxicityandCytokineResponses .......................... 12
7 AChallengefortheFuture:UnderstandingtheIntegrationofSignals
byNKCells ............................................ 13
References.................................................. 14
Abstract Theparticipationofnaturalkiller(NK)cellsinmultipleaspectsofinnate
andadaptiveimmuneresponsesissupportedbythewidearrayofstimulatoryand
inhibitoryreceptorstheybear.Herewereviewthereceptor-ligandinteractionsand
subsequentsignalingeventsthatculminateinNKeffectorresponses.Whereassome
receptor-ligandinteractionsresultinactivationofbothNKcytotoxicityandcytokine
2 C.A.Stewartetal.
production,othershavemoresubtleeffects,selectivelyactivatingonlyonepathway
orhavingdistinctcontext-dependenteffects.Recentapproachesofferwaystounravel
howtheintegrationofcomplexsignalingnetworksdirectstheNKresponse.
1
Introduction
Natural killer (NK) cells are large granular lymphocytes of the innate im-
mune system. They are widespread throughout the body, being present in
both lymphoid organs and nonlymphoid peripheral tissues (Cooper et al.
2004;FerlazzoandMunz2004).NKcellsareinvolvedindirectinnateimmune
reactionsagainstviruses,bacteria,parasites,andothertriggersofpathology,
suchasmalignanttransformation,allofwhichcausestressinaffectedcells
(Morettaetal.2002;Raulet2004).Importantly,NKcellsalsolinktheinnate
andadaptiveimmuneresponses,contributingtotheinitiationofadaptiveim-
muneresponses(seechapterbyZitvogeletal.,thisvolume)(Martin-Fontecha
γ
et al. 2004) and executing adaptive responses with the CD16 Fc RIIIA im-
munoglobulinFcreceptor.Suchresponsesaremediatedthroughtwomajor
effectorfunctions,thedirectcytolysisoftargetcellsandtheproductionofcy-
tokinesandchemokines.Wefocushereonthenatureofrecognitioneventsby
NKcellsandaddresshowtheseeventsareintegratedtotriggerthesedistinct
andgradedeffectorfunctions.
2
ThemesofNKCellRecognition
The dissection of NK cell innate recognition strategies was initiated by the
discoverythatNKcellcytotoxicityinverselycorrelateswiththelevelofmajor
histocompatibility complex (MHC)class Iexpression on target cells (Karre
etal.1986).Themissingselfhypothesiselegantlyprovidedanexplanationfor
this phenomenon and led to the discovery of multiple inhibitory receptors
thatblockactivatingsignalsbyrecruitmentofproteintyrosinephosphatases
totheirintracytoplasmicimmunoreceptortyrosine-basedinhibitionmotifs
(ITIMs)(Long1999;VivierandDaëron1997).Opposingthisinhibitorysig-
naling,innatestimulatoryrecognitionbyNKcellscanbeclassifiedinthree
generalmodes:recognitionofconstitutivelyexpressedselfmolecules,recog-
nitionofmotifsupregulatedbystressedcells,anddirectrecognitionofinfec-
tiouspathogencomponents(Raulet2004;VivierandMalissen2005).Together,
StrategiesofNaturalKillerCellRecognition andSignaling 3
thenumerous receptors carrying out these functions allow NK cells to dis-
criminatebetweentargetandnon-targetcells(Fig.1)(CerwenkaandLanier
2001;VilchesandParham2002;VivierandBiron2002;Yokoyama1998).Only
aminorityofthesereceptors,suchasthenaturalcytotoxicityreceptors(NCR),
aretrulyNKcellspecific,withmanybeingfoundonotherhematopoieticcells.
Thequestionofhowallthesignalsareintegratedfrommultiple,redundant
andopposing,simultaneouslyengagedpathwaystoculminateingradedNK
cellresponses,thatis,cytotoxicityand/orcytokineproduction,servestoillus-
tratethecomplexanddynamicallybalancednatureofcellactivation(Lanier
2003;Vivieretal.2004).
3
InhibitoryRecognitionandSignaling
3.1
InhibitoryReceptorsforMHCClassI
Multiple families of receptors in mouse and human recognize MHC class
I products and transmit inhibitory signals when engaged. CD94/NKG2
receptorsareheterodimersofC-typelectintypeIItransmembraneproteins
that recognize the nonclassical MHC class I molecules HLA-E (human
leukocyteantigen-E,inhuman)andQa-1b (inmouse)(Borregoetal.1998;
Braud et al. 1998; Lee et al. 1998; Vance et al. 1998). Of the NKG2 family
members that associate with CD94 (including NKG2A, C, and E), NKG2A
contains ITIMs in its cytoplasmic domain conferring inhibitory function.
Recognition of HLA-E or Qa-1b by CD94/NKG2 requires the presence of
peptidesinthepeptidebindinggroovesoftheseclassImolecules.Manyof
thesepeptidesarederivedfromtheleadersequencesofclassicalMHCclass
Imolecules(Braudetal.1997;Kraftetal.2000),thusmakingCD94/NKG2A
a sensor of active MHC class I biosynthesis and presentation. CD94/NKG2
is unique in both its high evolutionary conservation and its means of
recognizingclassicalMHCclassIasa“proxy”sensor.
MembersofotherNKcellMHCclassIreceptorfamiliesdirectlybindto
classicalMHCclassImolecules.Inthemouseandrat,NKcellrecognitionof
subsetsofMHCclassIallotypesismediatedbymembersoftheLy49family
ofC-typelectintypeIItransmembraneproteins.Incontrast,humanNKcells
useimmunoglobulindomain-containingtypeItransmembraneproteinsfor
thesamefunction.Theimmunoglobulin-liketranscript2(ILT2,orLIR1)re-
ceptorrecognizesabroadrangeofbothclassicalandnonclassicalMHCclass
I molecules (Chapman et al. 1999; Colonna et al. 1997), whereas members
4 C.A.Stewartetal.
Fig.1 ThemesinNKcellrecognitionandsignaling.NKreceptorscanbeclassified
according to their recognition of ligands expressed by self cells, stressed cells, or
pathogens. Prototypical receptor-ligand interactions that are described in the text
areshown.Additionalligandsareknownforanumberofthereceptorsshown.Ef-
fectsoftheseinteractionsaredetailedasinhibitory(−),activating(+),orinvolved
inadhesion.Themotifsusedbymembranereceptorsorassociatedsignalingadap-
tormoleculesareshownforeachreceptor.Theseservetoillustratetheassociation
ofmanyNKactivatingreceptorswithspecializedsignalingtransmembraneadaptor
proteinsthatcontainITAMs(immunoreceptortyrosine-basedactivationmotifs)or
YINM motifs in their cytoplasmic tails. These adaptors form homodimers or het-
erodimersthroughdisulfidebondingandassociatewithmembranereceptorsusing
chargedaminoacidsinthetransmembranedomain(stars;whiteindicatespositive
charge,redindicatesnegativecharge).OthermotifsincludingITIM(immunoreceptor
tyrosine-basedinhibitorymotif)andITSM(immunoreceptortyrosine-basedswitch
γ
motif) are found within the cytoplasmic domains of NK receptors. The Fc RIIIA
(CD16)receptorcouldbeclassifiedasrecognizingconstitutiveself,stressedself,or
pathogen-expressedmoietiesdependingonaparticularIgGantibody.AsIgGantibod-
iesrecognizingconstitutiveselfmoleculesarefrequentlyavoidedthroughprocessesof
γ
immunetolerance,Fc RIIIAisclassifiedhereasrecognizingpathogencomponents.
The figure includes both human and murine molecules that are not always found
intheotherspecies.Otherimportantabbreviations:MHC-I,majorhistocompatibil-
itycomplexclassImolecule;MICA,MHCclassIchain-relatedproteinA;Influenza
HA:influenzavirushemagglutinin;MCMV,murinecytomegalovirus;TLR,Toll-like
receptor.DirectinteractionandinhibitorymodulationofNKp30bypp65ofhuman
cytomegalovirushasbeendescribed(Arnonetal.2005).Therefore,NKp30mayalso
bedefinedasrecognizingpathogencomponents