人类白细胞抗原-HLA分型技术

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1、HLA分型技术上海交通大学医学院彭奕冰主任技师1MajorHistocompatibilityComplex(MHC)WhatisMHC?HLAH-2Minorhistocompatibilityantigens2SignificanceoftheMHCroleinimmuneresponseroleinorgantransplantationroleinpredispositiontodisease3Progressinorgantransplantation4Geneticbarrierstotransplantationautologous:inthesameindi

2、vidual(autograft)isologous:betweengeneticallyIdenticalindividuals(isograft),i.e.,identicaltwins(inbredanimals)homologous:betweenindividualsofthesamespecies(allograft)heterologous:betweenindividualsdifferentspecies(xenograft)5Principlesoftransplantation6Minorhistocompatibilityantigensandgra

3、ftsurvivalminorhistocompatibilityantigensalsocauserejectionTherejectiontimeisvariablebutlongerthanthatformajorhistocompatibilityantigenTheyhaveadditiveeffects7Graftversushost(GVH)disease8GVHdiseaseinhumans9ThehumanMHCgenes10ThemouseMHCgenes11PolymorphismofMHCantigens(basedonphenotype)HLA基因系

4、统的多态性及一些主要基因座位的等位基因数正式命名显示多态性的HLA基因座位有31个，共2320个等位基因。 图中所示为常见基因座位的等位基因数。12TheinheritanceofMHCgenes13Crossingoverresultsinnewhaplotypes14MHCproductsexpressedoncellsIfJackandJillhavefourchildren;Bo,Kim,MoandLeeThey’llallinheritantigensoftheparentalMHCOfttheirhaplotypeswillbeofthefatherormoth

5、erUnlessduringmeiosis,acrossovershouldoccur15Class-Iexpressedonallnucleatedcellsinman,andalsoonerythrocytesinmice.Class-IIexpressedprimarilyonantigenpresentingcells(dendriticcells,macrophagesandBcells,etc.)DifferentialexpressionofMHCantigens16AlloreactivityofTcells:MLRandCTLgenerationCD4+TH

6、1CD8+CTLCD8+preCTL17AlloreactivityofTcellsPositiveSelectionThymusAlloreaction(MLR)ProliferationandDifferentiation18InflammationlysisADCClysisIL2,IFNTNF,NO2IL2,IL4,IL5IL2,TNF,IFNrejectionMechanismsofgraftrejection19Tempoofrejectionreactiontypeofrejectiontimetakencausechronicmonths-yearsu

7、nclearcauses:crossreactiveAb,immunecomplexes,slowcellularreaction,tolerancebreakdown,diseaserecurrenceaccelerateddaysreactivationofsensitizedTcells(secondaryresponse)acutedays-weeksprimaryactivationofTcellshyperacuteminutes-hourspreformedanti-donorantibo