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Immunology

Unmasking the killer's accomplice

Nature volume 391, pages 642–643 (1998)Cite this article

Class I molecules of the major histocompatibility complex (MHC) are polymorphic glycoproteins which, under normal circumstances, are expressed on the surface of almost every cell in the body. Upon viral infection or in tumour cells, however, MHC class I can be downregulated, and its absence is ‘sensed’ by natural killer (NK) cells in a process known as recognition of ‘missing self’1. This is mediated by cell-surface receptors which, on binding class I molecules, transduce inhibitory signals that block NK-cell-mediated lysis. When class I expression is lost or reduced, NK cells are released from inhibition and can, therefore, rapidly identify and eliminate virally infected or tumour cells.

Intriguingly, some MHC class I NK-cell-receptor homologues promote — rather than inhibit — the activation and cytotoxicity of NK cells, by a hitherto unknown mechanism. But on page 703 of this issue, Lanier et al.2 describe the key to this mystery. They have discovered a signal-transducing molecule called DAP12, which couples an MHC class I receptor on the surface of the NK cell to an activating signal-transduction pathway within that cell.

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Figure 1: Structure of the activating natural killer (NK)-cell receptor complex for major histocompatibility complex (MHC) class I molecules.
Figure 2: Hypothetical interactions between activating and inhibitory MHC class I receptors.

References

  1. Ljunggren, H. G. & Kärre, K. Immunol. Today 11, 237–244 (1990).

    Google Scholar 

  2. Lanier, L. L., Corliss, B. C., Wu, J., Leong, C. & Phillips, J. H. Nature 391, 703–707 (1998).

    Article  ADS  CAS  Google Scholar 

  3. Yokoyama, W. M. Curr. Biol. 5, 982–985 (1995).

    Google Scholar 

  4. Lanier, L. L. Immunity 6, 371–378 (1997).

    Google Scholar 

  5. Leibson, P. J. Immunity 6, 655–661 (1997).

    Google Scholar 

  6. Mason, L. H.et al. J. Exp. Med. 184, 2119–2128 (1996).

    Google Scholar 

  7. Houchins, J. P., Lanier, L. L., Niemi, E., Phillips, J. H. & Ryan, J. C. J. Immunol. 158, 3603–3609 (1997).

    Google Scholar 

  8. Moretta, A.et al. J. Exp. Med. 182, 875–884 (1995).

    Google Scholar 

  9. Biassoni, R.et al. J. Exp. Med. 183, 645–650 (1996).

    Google Scholar 

  10. Weiss, A. & Littman, D. R. Cell 76, 263–274 (1994).

    Google Scholar 

  11. Olcese, L.et al. J. Immunol. 158, 5083–5086 (1997).

    Google Scholar 

  12. Samaridis, J. & Colonna, M. Eur. J. Immunol. 27, 660–665 (1996).

    Google Scholar 

  13. Takase, K.et al. J. Immunol. 159, 741–747 (1997).

    Google Scholar 

  14. Kärre, K. & Welsh, R. M. Nature 386, 446–447 (1997).

    Article  ADS  Google Scholar 

Download references

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  1. Marco Colonna is at the Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005, Basel, Switzerland

    Marco Colonna

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  1. Marco Colonna
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Colonna, M. Unmasking the killer's accomplice. Nature 391, 642–643 (1998). https://doi.org/10.1038/35515

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