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RESEARCH PRODUCT
Presentation of an Immunodominant Immediate-Early CD8+ T Cell Epitope Resists Human Cytomegalovirus Immunoevasion.
Bodo PlachterMichael NeuenhahnDirk H. BuschFabian SchlottAndreas MoosmannJosef MautnerStefanie Ameressubject
Cytomegalovirus InfectionMaleViral DiseasesvirusesCytomegalovirusEpitopes T-LymphocyteNK cellsAdaptive ImmunityCD8-Positive T-LymphocytesMajor Histocompatibility ComplexInterleukin 21Viral Envelope ProteinsCytotoxic T celllcsh:QH301-705.5Antigen PresentationbiologyViral Immune EvasionImmune cellsRNA-Binding ProteinsInnate ImmunityKiller Cells Naturalmedicine.anatomical_structureInfectious DiseasesCytomegalovirus InfectionsMedicineFemaleResearch Articlelcsh:Immunologic diseases. AllergyT cellImmunologyCD1T cells610StreptamerMicrobiologyImmediate-Early ProteinsImmunomodulationViral ProteinsVirologyMHC class IGeneticsmedicineHumansAntigen-presenting cellMolecular BiologyBiologyImmune EvasionHistocompatibility Antigens Class IImmunityMHC restrictionVirologyProtein Structure Tertiarylcsh:Biology (General)Immunologybiology.proteinParasitologylcsh:RC581-607description
Control of human cytomegalovirus (HCMV) depends on CD8+ T cell responses that are shaped by an individual's repertoire of MHC molecules. MHC class I presentation is modulated by a set of HCMV-encoded proteins. Here we show that HCMV immunoevasins differentially impair T cell recognition of epitopes from the same viral antigen, immediate-early 1 (IE-1), that are presented by different MHC class I allotypes. In the presence of immunoevasins, HLA-A- and HLA-B-restricted T cell clones were ineffective, but HLA-C*0702-restricted T cell clones recognized and killed infected cells. Resistance of HLA-C*0702 to viral immunoevasins US2 and US11 was mediated by the alpha3 domain and C-terminal region of the HLA heavy chain. In healthy donors, HLA-C*0702-restricted T cells dominated the T cell response to IE-1. The same HLA-C allotype specifically protected infected cells from attack by NK cells that expressed a corresponding HLA-C-specific KIR. Thus, allotype-specific viral immunoevasion allows HCMV to escape control by NK cells and HLA-A- and HLA-B-restricted T cells, while the virus becomes selectively vulnerable to an immunodominant population of HLA-C-restricted T cells. Our work identifies a T cell population that may be of particular efficiency in HCMV-specific immunotherapy.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-05-01 |