title: Presentation of an immunodominant immediate-early CD8+ T cell epitope resists human cytomegalovirus immunoevasion.
abstract: 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.
authors.affiliation: Clinical Cooperation Group Immunooncology, Department of Medicine III, Klinikum der Universität München, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ameres
authors.forename: Josef
authors.initials: J
authors.lastname: Mautner
authors.forename: Fabian
authors.initials: F
authors.lastname: Schlott
authors.forename: Michael
authors.initials: M
authors.lastname: Neuenhahn
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.forename: Bodo
authors.initials: B
authors.lastname: Plachter
authors.forename: Andreas
authors.initials: A
authors.lastname: Moosmann
mesh_terms: D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology; D057131:Immune Evasion; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008297:Male; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; C118670:US2 protein, Varicellovirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins