title: Natural killer cells activated by MHC class I(low) targets prime dendritic cells to induce protective CD8 T cell responses.
abstract: Conserved molecular patterns derived from pathogenic microorganisms prime antigen-presenting dendritic cells (DC) to induce adaptive T cell responses. In contrast, virus-infected or tumor cells that express low levels of major histocompatibility complex (MHC) class I activate natural killer (NK) cells for direct killing. It is unknown whether NK cell recognition of MHC class I(low) targets can also induce adaptive T cell responses. Here, we show that MHC class I(low) targets initiate a cascade of immune responses, starting with the immediate activation of NK cells. The activated NK cells then prime DC to produce IL-12 and to induce highly protective CD8 T cell memory responses. Therefore, sensing of MHC class I(low) targets by NK cells can link innate and adaptive immunity to induce protective T cell responses and may alarm the immune system during early infection with noncytopathic viruses.
authors.affiliation: GSF-Institut für Molekulare Immunologie, 81377 Munich, Germany. mocikat@gsf.de
authors.forename: Ralph
authors.initials: R
authors.lastname: Mocikat
authors.forename: Heidi
authors.initials: H
authors.lastname: Braumüller
authors.forename: Alain
authors.initials: A
authors.lastname: Gumy
authors.forename: Oliver
authors.initials: O
authors.lastname: Egeter
authors.forename: Heike
authors.initials: H
authors.lastname: Ziegler
authors.forename: Uwe
authors.initials: U
authors.lastname: Reusch
authors.forename: Anja
authors.initials: A
authors.lastname: Bubeck
authors.forename: Jacques
authors.initials: J
authors.lastname: Louis
authors.forename: Reinhard
authors.initials: R
authors.lastname: Mailhammer
authors.forename: Gert
authors.initials: G
authors.lastname: Riethmüller
authors.forename: Ulrich
authors.initials: U
authors.lastname: Koszinowski
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002277:Carcinoma / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D008223:Lymphoma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I