MHC Class I-Presented T Cell Epitopes Identified by Immunoproteomics Analysis Are Targets for a Cross Reactive Influenza-Specific T Cell Response 英文参考文献.docVIP

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MHC Class I-Presented T Cell Epitopes Identified by Immunoproteomics Analysis Are Targets for a Cross Reactive Influenza-Specific T Cell Response 英文参考文献.doc

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MHC Class I-Presented T Cell Epitopes Identified by Immunoproteomics Analysis Are Targets for a Cross Reactive Influenza-Specific T Cell Response 英文参考文献

MHCClassI-PresentedTCellEpitopesIdentifiedby ImmunoproteomicsAnalysisAreTargetsforaCross ReactiveInfluenza-SpecificTCellResponse JamesS.Testa,VivekanandaShetty,JulieHafner,ZacharieNickens,ShivaliKamal, GomathinayagamSinnathamby,RamilaPhilip* Immunotope,Inc.,Doylestown,Pennsylvania,UnitedStatesofAmerica Abstract Influenzavirusinfectionandtheresultingcomplicationsareasignificantglobalpublichealthproblem.Improvinghumoral immunity to influenza is the target of current conventional influenza vaccines, however, these are generally not cross- protective. On the contrary, cell-mediated immunity generated by primary influenza infection provides substantial protectionagainstserologicallydistinctvirusesduetorecognitionofcross-reactiveTcellepitopes,oftenfrominternalviral proteinsconservedbetweenviralsubtypes.Effortsareunderwaytodevelopauniversalfluvaccinethatwouldstimulate both the humoral and cellular immune responses leading to long-lived memory. Such a universal vaccine should target conserved influenza virus antibody and T cell epitopes that do not vary from strain to strain. In the last decade, immunoproteomics,orthedirectidentificationofHLAclassIpresentedepitopes,hasemergedasanalternativetothemotif prediction method for the identification of T cell epitopes. In this study, we used this method to uncover several cross- specific MHC class I specific T cell epitopes naturally presented by influenza A-infected cells. These conserved T cell epitopes, when combined with a cross-reactive antibody epitope from the ectodomain of influenza M2, generate cross- strainspecificcellmediatedandhumoralimmunity.Overall,wehavedemonstratedthatconservedepitope-specificCTLs couldrecognizemultipleinfluenzastraininfectedtargetcellsand,whencombinedwithauniversalantibodyepitope,could generatevirusspecifichumoralandTcellresponses,asteptowardauniversalvaccineconcept.Theseepitopesalsohave potentialasnewtoolstocharacterizeTcellimmunityininfluenzainfection,andmayserveaspartofauniversalvaccine candidate