title: Deletion mutant of human cytomegalovirus lacking US2-US6 and US11 maintains MHC class I expression and antigen presentation by infected dendritic cells.
abstract: A HCMV mutant of endothelial- and DC-tropic strain TB40/E lacking the described MHC downregulating genes US2-6 and US11 (RVTB40/E(4)ΔUS11) was generated. We analyzed the susceptibility of DC to RVTB40/E(4)ΔUS11 and subsequently studied antigen presentation and T-cell stimulation. Wildtype TB40/E- and RVTB40/E(4)ΔUS11 showed no significant difference in the efficiency of infection of DC. Whereas infection with TB40/E induced downregulation of MHC I, no significant MHC I downregulation was observed on RVTB40/E(4)ΔUS11-infected DC, indicating that the US2-6, US11 region encodes for the major genes relevant for MHC I downregulation. However, both viruses induced downregulation of MHC II, as well as CD40, CD80, CD86 and CD83 to the same levels. Stimulation of IFN-γ production by HCMV-specific CD8+ T-cells by infected autologous DC correlated with the modulation of MHC expression. While TB40/E-infected DC did not efficiently stimulate IFN-γ production, RVTB40/E(4)ΔUS11-infected DC efficiently stimulated CD8+ T-cells to produce IFN-γ.
authors.affiliation: Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten, Eberhard-Karls-Universität Tübingen, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schempp
authors.forename: Max
authors.initials: M
authors.lastname: Topp
authors.forename: Tobias
authors.initials: T
authors.lastname: Kessler
authors.forename: Kerstin Laib
authors.initials: KL
authors.lastname: Sampaio
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Dennehy
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hahn
authors.forename: Götz Ulrich
authors.initials: GU
authors.lastname: Grigoleit
authors.forename: Gerhard
authors.initials: G
authors.lastname: Jahn
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D017384:Sequence Deletion
chemical_list: D015395:Histocompatibility Antigens Class I