title: Acquisition of MHC:peptide complexes by dendritic cells contributes to the generation of antiviral CD8+ T cell immunity in vivo.
abstract: There is an increasing body of evidence suggesting that the transfer of preformed MHC class I:peptide complexes between a virus-infected cell and an uninfected APC, termed cross-dressing, represents an important mechanism of Ag presentation to CD8+ T cells in host defense. However, although it has been shown that memory CD8+ T cells can be activated by uninfected dendritic cells (DCs) cross-dressed by Ag from virus-infected parenchymal cells, it is unknown whether conditions exist during virus infection in which naive CD8+ T cells are primed and differentiate to cytolytic effectors through cross-dressing, and indeed which DC subset would be responsible. In this study, we determine whether the transfer of MHC class I:peptide complexes between infected and uninfected murine DC plays a role in CD8+ T cell priming to viral Ags in vivo. We show that MHC class I:peptide complexes from peptide-pulsed or virus-infected DCs are indeed acquired by splenic CD8α⁻ DCs in vivo. Furthermore, the acquired MHC class I:peptide complexes are functional in that they induced Ag-specific CD8+ T cell effectors with cytolytic function. As CD8α⁻ DCs are poor cross-presenters, this may represent the main mechanism by which CD8α⁻ DCs present exogenously encountered Ag to CD8+ T cells. The sharing of Ag as preformed MHC class I:peptide complexes between infected and uninfected DCs without the restraints of Ag processing may have evolved to accurately amplify the response and also engage multiple DC subsets critical in the generation of strong antiviral immunity.
authors: Medical Research Council Centre for Transplantation, King's College London, London SE1 9RT, United Kingdom. lesley.smyth@kcl.ac.uk
authors: Lesley A
authors: LA
authors: Smyth
authors: Catherine
authors: C
authors: Hervouet
authors: Thomas
authors: T
authors: Hayday
authors: Pablo D
authors: PD
authors: Becker
authors: Richard
authors: R
authors: Ellis
authors: Robert I
authors: RI
authors: Lechler
authors: Giovanna
authors: G
authors: Lombardi
authors: Linda S
authors: LS
authors: Klavinskis
mesh_terms: D000256:Adenoviridae / Q000276:immunology / Q000378:metabolism; D019264:Adoptive Transfer; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D007111:Immunity, Cellular; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin