Natural killer cells activated by MHC class I(low) targets prime dendritic cells to induce protective CD8 T cell responses.
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.
Mocikat
Ralph
R
GSF-Institut für Molekulare Immunologie, 81377 Munich, Germany. mocikat@gsf.de
Braumüller
Heidi
H
Gumy
Alain
A
Egeter
Oliver
O
Ziegler
Heike
H
Reusch
Uwe
U
Bubeck
Anja
A
Louis
Jacques
J
Mailhammer
Reinhard
R
Riethmüller
Gert
G
Koszinowski
Ulrich
U
Röcken
Martin
M
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
D015395:Histocompatibility Antigens Class I