a dominant role for the immunoproteasome in cd8+ t cell responses to murine cytomegalovirus主导作用的immunoproteasome cd8 + t细胞对小鼠巨细胞病毒的反应.pdfVIP

A Dominant Role for the Immunoproteasome in CD8+ T Cell Responses to Murine Cytomegalovirus 1 1 1 2 2 2 Sarah Hutchinson , Stuart Sims , Geraldine O’Hara , Jon Silk , Uzi Gileadi , Vincenzo Cerundolo , Paul Klenerman1* 1 Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom, 2 Weatherall Institute of Molecular Medicine, Molecular Immunology Group, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom Abstract Murine cytomegalovirus (MCMV) is an important animal model of human cytomegalovirus (HCMV), a b-Herpesvirus that infects the majority of the world’s population and causes disease in neonates and immunocompromised adults. CD8+ T cells are a major part of the immune response to MCMV and HCMV. Processing of peptides for presentation to CD8+ T cells may be critically dependent on the immunoproteasome, expression of which is affected by MCMV. However, the overall importance of the immunoproteasome in the generation of immunodominant peptides from MCMV is not known. We therefore examined the role of the immunoproteasome in stimulation of CD8+ T cell responses to MCMV – both conventional memory responses and those undergoing long-term expansion or ‘‘inflation’’. We infected LMP72/ 2 and C57BL/6 mice with MCMV or with newly-generated recombinant vaccinia viruses (rVVs) encoding the immunodominant MCMV protein M45 in either full-length or epitope-only minigene form. We analysed CD8+ T cell responses using intracellular cytokine stain (ICS) and MHC Class I tetramer stainin