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Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom
Recently, it has become apparent that surface proteins commonly transfer between immune cells in contact. Inhibitory receptors and ligands exchange between cells during NK cell surveillance and we report here that NK cells also acquire activating ligands from target cells. Specifically, the stress-inducible activating ligand for NKG2D, MHC class I-related chain A (MICA), transferred to NK cells upon conjugation with MICA-expressing target cells. Acquisition of MICA from target cells was dependent on cell contact and occurred after accumulation of MICA at the immunological synapse. Moreover, transfer of MICA was facilitated by specific molecular recognition via NKG2D and augmented by Src kinase signaling. Importantly, MICA associated with its new host NK cell membrane in an orientation that allowed engagement with NKG2D in trans and indeed could down-regulate NKG2D in subsequent homotypic interactions with other NK cells. MICA captured from target cells could subsequently transfer between NK cells and, more importantly, NK cell degranulation was triggered in such NK cell-NK cell interactions. Thus, NK cells can influence other NK cells with proteins acquired from target cells and our data specifically suggest that NK cells could lyse other NK cells upon recognition of activating ligands acquired from target cells. This mechanism could constitute an important function for immunoregulation of NK cell activity.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Medical Research Council, the Biotechnology and Biological Science Research Council, a Lister Institute Research Prize (to D.M.D.), and by a fellowship from The Wenner-Gren Foundations (to B.Ö.).
2 F.E.M. and P.E. contributed equally to this work.
3 Current address: Kennedy Institute of Rheumatology, Imperial College London, 1 Aspenlea Road, London W6 8LH, U.K.
4 Current address: Strategic Research Center for Studies of Integrative Recognition in the Immune System, Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, S-171 77 Stockholm, Sweden.
5 Address correspondence and reprint requests Dr. Daniel M. Davis, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, U.K. E-mail address: d.davis{at}imperial.ac.uk
6 Abbreviations used in this paper: MICA, MHC class I-related chain A; ULBP, UL-16 binding protein; YFP, yellow fluorescent protein; MFI, mean fluorescence intensity; KIR, killer Ig-related receptor; CFP, cyan fluorescent protein.
7 The online version of this article contains supplemental material.
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