T細胞受體CDR3δ移植性抗體（OT3）—免疫毒素的抗腫瘤研究及CDR3δ多肽的構象研究.pdf

1、Y1414290中國坼和醫(yī)科大學博士學位畢業(yè)論文T細胞受體cDR36移植性抗體(oT3)一免疫毒素的抗腫瘤研究及CDR36多肽的構象研究研究生：王準導師：何維教授崔蓮仙教授學科專業(yè)：免疫學研究方向：腫瘤免疫入學時間：2003年9月所在院所：中國協(xié)和醫(yī)科大學基礎醫(yī)學院中國醫(yī)學科學院基礎醫(yī)學研究所2006年11月北京中國協(xié)和醫(yī)科大學博士學位畢業(yè)論文英文摘要Abstract丫6TcellshaVeabroadantitumorspectrum

2、withdistinctantigenrecognitionmechanismfbmⅡpTcells鋤dimmunoglobulins丫6TCRrecognizesantigensinawaylikepanemrecognitionreceptorSThespecific時鋤da銜nityof丫6TceHreceptor(丫6TCR)liesinitsCDR36，theComplementa叮DeterminantRegion3of6c

3、hainInourpIeviousStudies，theoT3peptide，whosesequencewasf硒mCDR36ofovariancancerinfiltrated丫6TceIls，couldbindwithmanykindsoftumorcelllinesandtissuesInthisexperiment’appIicationofanoVelantibodyinexperimentaIoncologywasevalu

4、ated，whoseCDR3HisreplacedbysequenceofoT3First，thisantibodynamedoT3Ab、^，asexpressedbymurineJ558LmyelomaTheheaVychainwithCDR36camefbmhumanIgGlexpressionVectorPNl，lVH62CDR36andlightchain、Ⅳasf硒mJ558LcellsA舭rreducingsodiumdod

5、ecylsulfatepolyac呵l鋤idegelelectrophoresis(SDSPAGE)鋤dWestemblottingconfimation，OT3Abexhibitedspecif：icbindingwithoVariancancercenlineSKOV3bynowc”omtry砌’，加DexperimentalsodemonstratedoT3AbcouIdmediateantibodydependentcellme

6、diatedcytotoxicityagainstSKoV3cellline如1，加mdioisptopeimaginginnudemicebearingSKoV3tumorsshowedta唱etingof9咖TclabeledoT3AbtotumortissueThen觚immunotoxinoT3AbDTwasconstructedbychemicallyconjugationofoT3Abanddiphtheriatoxin(D

7、DARerpurificationthl’oughhighpeI。fomanceliquidchromatography(HPLC)onasizeexclusioncolumn，non—reducingSDSPAGEandWbStemblottingwerecarriedoutt0confirmthesuccess凡lconjugationThebindingabili鑼ofoT3AbDTwithSKoV3ceIlswasnotaffe