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PNAS 101 (48): 16873-16878

Copyright © 2004 by the National Academy of Sciences.

IMMUNOLOGY

Human and murine inhibitory natural killer cell receptors transfer from natural killer cells to target cells

Bruno Vanherberghen *, {dagger}, Katja Andersson {dagger}, Leo M. Carlin *, Esther N. M. Nolte-`t Hoen *, Geoffrey S. Williams *, Petter Höglund {dagger} {ddagger}, §, and Daniel M. Davis * {ddagger}, §

*Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College, London SW7 2AZ, United Kingdom; and {dagger}Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, S-171 77 Stockholm, Sweden

Edited by Philippa Marrack, National Jewish Medical and Research Center, Denver, CO

Accepted for publication October 15, 2004.

Received for publication August 24, 2004.

Abstract: Intercellular transfer of proteins across the immunological synapse is emerging as a common outcome of immune surveillance. We previously reported that target-cell MHC class I protein transfers onto natural killer (NK) cells expressing cognate killer Ig-like receptors (KIRs). We now show that, for both murine and human cells, target cells expressing inhibitory MHC class I ligands acquire cognate inhibitory NK receptors. Other cell-surface proteins, but not a cytoplasmic dye, also transferred from human NK cells to target cells across an inhibitory immunological synapse. The number of KIRs acquired from NK cells correlated with the level of expression of cognate MHC class I protein on target cells. Treatment with cytoskeletal inhibitors demonstrated that the target-cell cytoskeleton influences intercellular transfer of proteins in both directions. In contrast to constitutively expressed KIRs, a fraction of acquired KIRs could be removed by mild acid wash, demonstrating a difference between some of the acquired KIRs and constitutively expressed KIRs. An accumulation of phosphotyrosine at the location of the transferred KIRs implies a signaling capacity for NK cell proteins transferred to target cells. Thus, intercellular protein transfer between immune cells is bidirectional and could facilitate new aspects of immune cell communication.

Key Words: imaging • immunological synapse

Author contributions: B.V., K.A., L.M.C., E.N.M.N.-t.H., G.S.W., P.H., and D.M.D. designed research; B.V., K.A., E.N.M.N.-t.H., and G.S.W. performed research; B.V., K.A., L.M.C., E.N.M.N.-t.H., G.S.W., P.H., and D.M.D. analyzed data; and B.V., P.H., and D.M.D. wrote the paper.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: NK, natural killer; KIR, killer Ig-like receptor; IS, immune synapse; DiD, 1,1'dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine, 4-chlorobenzene-sulfonate salt; LSCM, laser-scanning confocal microscopy; MFI, median fluorescence intensity; EL4-Dd-GFP, EL4 transfected to express H-2Dd protein tagged with GFP; LAK, lymphokine-activated killer; HRP, horseradish peroxidase.

{ddagger} P.H. and D.M.D. contributed equally to this work.

§ To whom correspondence may be addressed. E-mail: d.davis{at}imperial.ac.uk. or petter.hoglund{at}mtc.ki.se.

© 2004 by The National Academy of Sciences of the USA

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