Ex Vivo SIV-Specific CD8 T Cell Responses in Heterozygous Animals Are Primarily Directed against Peptides Presented by a Single MHC Haplotype 英文参考文献.docVIP

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Ex Vivo SIV-Specific CD8 T Cell Responses in Heterozygous Animals Are Primarily Directed against Peptides Presented by a Single MHC Haplotype 英文参考文献.doc

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Ex Vivo SIV-Specific CD8 T Cell Responses in Heterozygous Animals Are Primarily Directed against Peptides Presented by a Single MHC Haplotype 英文参考文献

ExVivoSIV-SpecificCD8TCellResponsesin HeterozygousAnimalsArePrimarilyDirectedagainst PeptidesPresentedbyaSingleMHCHaplotype JustinM.Greene1,EmilyN.Chin2,MelisaL.Budde3,JenniferJ.Lhost1,PaulJ.Hines3, BenjaminJ.Burwitz3,KarlW.Broman4,JenniferE.Nelson3,ThomasC.Friedrich3,5, DavidH.O’Connor1,2,3 * 1Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 2Department of Cellular and MolecularBiology,UniversityofWisconsin-Madison,Madison,Wisconsin,UnitedStatesofAmerica,3WisconsinNationalPrimateResearchCenter,UniversityofWisconsin- Madison, Madison, Wisconsin, United States of America, 4Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, UnitedStatesofAmerica,5DepartmentofPathobiologicalSciences,UniversityofWisconsin,Madison,Wisconsin,UnitedStatesofAmerica Abstract ThepresenceofcertainMHCclassIallelesiscorrelatedwithremarkablecontrolofHIVandSIV,indicatingthatspecificCD8T cellresponsescaneffectivelyreduceviralreplication.Itremainsunclearwhetherepitopicbreadthisanimportantfeatureof thiscontrol.PreviousstudieshavesuggestedthatindividualsheterozygousattheMHCclassIlocisurvivelongerand/or progressmoreslowlythanthosewhoarehomozygousattheseloci,perhapsduetoincreasedbreadthoftheCD8Tcell response.We usedMauritian cynomolgusmacaques withdefined MHChaplotypesandviralinhibition assaystodirectly compare CD8 T cell efficacy in MHC-heterozygous and homozygous individuals. Surprisingly, we found that cells from heterozygotes suppress viral replication most effectively on target cells from animals homozygous for only one of two potentialhaplotypes.Thesameheterozygouseffectorcellsdidnoteffectivelyinhibitviralreplicationaseffectivelyonthe target cells homozygous for theother haplotype. These results indicate thatthe greater potential breadthof CD8 T cell responses present in heterozygous animals does not necessarily lead to greater antiviral efficacy and suggest th