ForaTcelltobeactivatedbyaspecificantigen,theTcellreceptormustrecognizecomplexesofMHCIwiththeantigenonthesurfaceofanantigen-presentingcell.TcellsandtheTcellreceptorcomplexdonotrespondtoantigeninsolution,butevenforthespecificantigentheyonlyrespondtoantigen-MHC-1complexesonthecellsurface.ThisinteractionisnecessaryforTcellactivation,butitisnotsufficient.Tcellactivationalsorequiresaco-stimulatorysignalinvolvinginteractionofCD28ontheTcellwithCD80orCD86(B7familygenes)ontheantigen-presentingcell.CD28activatesasignaltransductionpathwayactingthroughPI-3K,LckandGrb-2/ITKtoprovideitsco-stimulatorysignalforTcellactivation.AnothermeanstocontrolTcellactivationisbyexpressingfactorsthatdown-regulateTcellactivation.SignalingbyactivatedTcellreceptorsinducesexpressionofCTLA-4,areceptorthatopposesTcellactivation.CTLA-4hasahigheraffinitythanCD28forB7proteins,terminatingTcellactivation.ICOSisaproteinrelatedtoCD28thatisonlyexpressedonactivatedTcells,andthatprovidesanotherimportantco-stimulatorysignal.Therequirementforco-stimulatorysignalsprovidesadditionalcontrolmechanismsthatpreventinappropriateandhazardousTcellactivation.

Contributor:GlennCroston,PhD

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