Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells.
The activity of natural killer (NK) cells is regulated by surface receptors, which direct target cell recognition. NKp30 (Natural Cytotoxicity Receptor 3) induces target cell lysis and is also crucial for the interaction with dendritic cells. So far, the cellular ligands for NKp30 have remained elusive. Here we show that the nuclear factor HLA-B-associated transcript 3 (BAT3) was released from tumor cells, bound directly to NKp30, and engaged NKp30 on NK cells. BAT3 triggered NKp30-mediated cytotoxicity and was necessary for tumor rejection in a multiple myeloma model. These data identify BAT3 as a cellular ligand for NKp30. We propose a concept for target cell recognition by NK cells beyond "missing self" and "induced self," mediated through a tumor cell-derived extracellular factor.
Pogge von Strandmann
Elke
E
Department of Internal Medicine I, University Hospital of Cologne, Kerpener Str. 62, D-50924 Cologne, Germany. elke.pogge@uk-koeln.de
Simhadri
Venkateswara Rao
VR
von Tresckow
Bastian
B
Sasse
Stephanie
S
Reiners
Katrin S
KS
Hansen
Hinrich P
HP
Rothe
Achim
A
Böll
Boris
B
Simhadri
Vijaya Lakshmi
VL
Borchmann
Peter
P
McKinnon
Peter J
PJ
Hallek
Michael
M
Engert
Andreas
A
D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D018832:Molecular Chaperones; D009101:Multiple Myeloma / Q000276:immunology; D055628:Natural Cytotoxicity Triggering Receptor 3; D009369:Neoplasms / Q000276:immunology*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C092009:BAG6 protein, human; D018832:Molecular Chaperones; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D011506:Proteins; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma