HISOCOMAIBILIYCOMLEX主要组织相容性复合体

CHAPTER11

THEMAJORHISTOCOMPATIBILITYCOMPLEXIntroductionMajorhistocompatibilityantigensystemMajorhistocompatibilitycomplex:Alargegeneticlocusthatincludesthehighlypolymorphicgenesencodingthepeptide-bindingmoleculesrecognizedbyTlymphocytes.TheMHClocusalsoincludesgenesencodingcytokines,moleculesinvolvedinantigenprocessing,andcomplementproteins.H-2complex:murineMHCsHLA:humanMHCwhichisknownasthehumanleucocytesantigensystem.ThreeclassesofMHCgenescloselylinkedonchromosomeClassⅠgeneClassⅡgeneClassⅢgeneTheorganizationofmurineandhumanMHCMouseH-2complex:ClassⅠgene:K,DLclassⅠmolecules(αchain）ClassⅡgene:IclassⅡmolecules(αβchain)ClassⅢgene:Scomplement,TNFSKID/LChr.17centromereH-2HumanHLAcomplex:DPDNDODQDRBCEAGHLAcomplexcentromereChr.6classlociProteinsencodingHLAclassⅠClassicalB,C,AHLAclassⅠmoleculesNon-classicalE,F,GHLAclassⅡClassicalDP,DQ,DRHLAclassIⅠmoleculesNon-classicalDN,DOHLAclassⅢComplement,TNF,HSPGeneticsofMHCPolygenicPolymorphicHaplotypeinheritedCodominantHLA-ⅠⅠmoleculesThestructureandfunctionofMHCmoleculesStructureTwopolypeptidechain:H-chainandβ2-microglobulin(notcodedbytheMHC)Heavychainhas3domains:α1,α2,αα3.Heavychainαα1andα2domainsformthebindinggroove(thepolymorphicregion)α3domainbindtoCD8CellulardistibutionClassⅠmoleculesareexpressedonallnucleatedcells(allcellsexceptforRBC)ExistsintheformofMembraneboundmoleculesSolublemoleculesFunctionAntigenprocessingandpresenting(endogeneouspathway)peptidesgeneratedinthecytosol(eg.Virusantigen)becomeassociatedwithMHCclassⅠⅠmoleculeswhichmovetothesurfaceandcanberecognizedbyCD8+Tcell(cytotoxicTlymphocytes).InvolveintransplantrejectionTcelldevelopmentinthymusCytosolicpathogen(Endogenousantigen)Intravesicularpathogen(exogenousantigen)HLA-ⅡmoleculesStructureHeterodimersofααandββglycoproteinchains.Eachchainhas2domains(α1,α2andββ1,β2)α1andβ1formthebindinggroove.(thepolymorphicregion)CD4bindtoβ2domain2.CellulardistributionclassⅡⅡmoleculesareexpressedonBcellsMφDendriticcellsVascularendothelialcellsFunctionsAntigenprocessingandpresenting(exogeneouspathway):bothpathogensincellularvesiclesandthosecomefromoutsidethecellarepresentedonMHCclassⅡⅡmoleculesofAPCsandaretransportedtothecellsurfacewheretheycanberecognizedbyCD4+TcellInvolveintransplantrejectionRegulationofimmuneresponseTcelldevelopmentinthethymusNon-classicalHLA(HLA-ⅠⅠb)DifferentiationoractivationstatesDiseaseCytokinesFactorsinfluencingtheexpressionofHLAmolecules（1）内源性抗原原提呈：抗原原靶细细胞胞组成成HLAⅠⅠ类分分子子-抗原原肽肽复复合合物物表达达于于细细胞胞膜膜表表面面CD8+T细胞胞识识别别。。（2）外外源源性性抗抗原原提提呈呈：：抗原原APCHLAⅡⅡ类分分子子-抗原原肽肽复复合合物物表达达于于细细胞胞膜膜表表面面CD4+T细胞胞识识别别。HLA与疾疾病病的的关关系系（一一））R.R(relativerisk，相相对对危危险险率率)R.R值越越大大相相关关性性越越强强。。（二二））举举例例1.强直直性性脊脊柱柱炎炎与与B272.胰岛岛素素依依赖赖性性糖糖尿尿病病（（IDDM）与与DR3、DR4病人（（Ag+/Ag-）对照（（Ag+/Ag-）＝SignificanceofMHCControlofimmuneresponseMHCrestriction:TheabilityofTlymphocytestorespondonlywhentheyarepresentedwiththeappropriateantigeninassociationwitheither““self””MHCclassⅠⅠorclassⅡmolecules.Irgene(immuneresponsegene)血清学细胞学分子生物学实验方法补体介导的微量细胞毒试验混合淋巴细胞培养法（MLC)分子生物学技术原理抗体(HLA分型)+淋巴细胞(受者)+补体淋巴细胞受损判定结果（细胞死亡百分率）单向法双向法比较供、受者编码HLA抗原基因的DNA序列，判定供、受者间的相似程度。主要应用检测HLA-A、B、C抗原检测DR抗原HLA分型法法原理理及应应用GraftrejectionandtissuematchingAutoimmunediseasesusceptibilitySummuryKeypointsThedefinitionsofMHCandHLA.ThecompositionofHLAgenecomplexThestructure,distributionandfunctionsofMHCclassⅠandⅡⅡmolecules.9、静静夜夜四四无无邻邻，，荒荒居居旧旧业业贫贫。。。。12月月-2212月月-22Wednesday,December7,202210、雨中中黄叶叶树，，灯下下白头头人。。。22:08:4322:08:4322:0812/7/202210:08:43PM11、以我独沈沈久，愧君君相见频。。。12月-2222:08:4322:08Dec-2207-Dec-2212、故故人人江江海海别别，，几几度度隔隔山山川川。。。。22:08:4322:08:4322:08Wednesday,December7,202213、乍乍见见翻翻疑疑梦梦，，相相悲悲各各问问年年。。。。12月月-2212月月-2222:08:4322:08:43December7,202214、他乡生白发发，旧国见青青山。。07十二月月202210:08:43下午午22:08:4312月-2215、比不了得得就不比，，得不到的的就不要。。。。十二月2210:08下午12月-2222:08December7,202216、行动出成成果，工作作出财富。。。2022/12/722:08:4322:08:4307December202217、做前，，能够环环视四周周；做时时，你只只能或者者最好沿沿着以脚脚为起点点的射线线向前。。。10:08:43下下午10:08下下午22:08:4312月-229、没有失败，，只有暂时停停止成功！。。12月-2212月-22Wednesday,December7,202210、很多事情努努力了未必有有结果，但是是不努力却什什么改变也没没有。。22:08:4322:08:4322:0812/7/202210:08:43PM11、成功功就是是日复复一日日那一一点点点小小小努力力的积积累。。。12月月-2222:08:4322:08Dec-2207-Dec-2212、世间成成事，不不求其绝绝对圆满满，留一一份不足足，可得得无限完完美。。。22:08:4322:08:4322:08Wednesday,December7,202213、不知香香积寺，，数里入入云峰。。。12月-2212月-2222:08:4322:08:43December7,202214、意志坚强的的人能把世界界放在手中像像泥块一样任任意揉捏。07十二二月202210:08:43下下午22:08:4312月-2215、楚楚塞塞三三湘湘接接，，荆荆门门九九派派通通。。。。。十二二月月2210:08下下午午12月月-2222:08December7,202216、少少年年十十五五二二十十时时，，步步行行夺夺得得胡胡马马骑骑。。。。2022/12/722:08:4322:08:4307December202217、空山新雨后后，天气晚来来秋。。10:08:43下午午10:08下下午22:08:4312月-229、杨柳柳散和和风，，青山山澹吾吾虑。。。12月月-2212月月-22Wednesday,December7,202210、阅读读一切切好书书如同同和过过去最最杰出出的人人谈话话。22:08:4322:08:4322:0812/7/202210:08:43PM11、越是没有有本领的就就越加自命命不凡。12月-2222:08:4322:08Dec-2207-Dec-2212、越是无能的的人，越喜欢欢挑剔别人的的错儿。22:08:4322:08:4322:08Wednesday,Dece