Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Essay
  • Published:

Natural killer cell recognition of missing self

Nature Immunology volume 9, pages 477–480 (2008)Cite this article

The idea that NK cells can distinguish aberrant cells by recognizing 'absence of the expected', rather than 'presence of the unexpected' emerged more than 25 years ago. Klas Kärre recapitulates how the idea took shape, and the first five years of experimental work to test its general predictions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Kiessling, R., Klein, E. & Wigzell, H. 'Natural' killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cell. Specificity and distribution according to genotype. Eur. J. Immunol. 5, 112–117 (1975).

    Article  CAS  Google Scholar 

  2. Herberman, R.B., Nunn, M.E. & Lavrin, D.H. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity. Int. J. Cancer 16, 216–223 (1975).

    Article  CAS  Google Scholar 

  3. Snell, G. Histocompatibility genes of the mouse. II. Production and analysis of isogenic-resistant lines. J. Natl. Cancer Inst. 21, 843–877 (1958).

    CAS  PubMed  Google Scholar 

  4. Cudkowicz, G. & Bennet, M. Peculiar immunobiology of bone marrow allografts. I. Rejection of parental grafts by resistant F1 hybrid mice. J. Exp. Med. 134, 1513–1528 (1971).

    Article  CAS  Google Scholar 

  5. Kiessling, R. et al. Evidence for a similar or common mechanism for natural killer activity and resistance to hemopoietic grafts. Eur. J. Immunol. 7, 655–664 (1977).

    Article  CAS  Google Scholar 

  6. Kiessling, R., Petranyi, G., Klein, G. & Wigzell, H. Genetic variation of in vitro cytolytic activity and in vivo rejection potential of nonimmunized semisyngeneic mice against a mouse lymphoma line. Int. J. Cancer 15, 933–944 (1975).

    Article  CAS  Google Scholar 

  7. Welsh, R.M., Karre, K., Hansson, M., Kunkel, L.A. & Kiessling, R.W. Interferon-mediated protection of normal and tumor target cells against lysis by mouse natural killer cells. J. Immunol. 126, 219–225 (1981).

    CAS  PubMed  Google Scholar 

  8. Stern, P., Gidlund, M., Örn, A. & Wigzell, H. Natural killer cells mediate lysis of embryonal carcinoma cells lacking MHC. Nature 285, 341–342 (1980).

    Article  CAS  Google Scholar 

  9. Snell, G. Recognition structures determined by the H-2 complex. Transplant. Proc. 8, 147–152 (1976).

    CAS  PubMed  Google Scholar 

  10. De Baetselier, P., Katzav, S., Gorelik, E., Feldman, M. & Segal, S. Differential expression of H-2 gene products in tumour cells is associated with their metastatogenic properties. Nature 288, 179–181 (1980).

    Article  CAS  Google Scholar 

  11. Hildemann, W.H. Specific immunorecognition by histocompatibility markers: the original polymorphic system of immunoreactivity characteristic of all multicellular animals. Immunogenetics 5, 193–202 (1977).

    Article  Google Scholar 

  12. Kolb, H. On the phylogenetic origin of the immune system – a hypothesis. Dev. Comp. Immunol. 1, 193–206 (1977).

    Article  CAS  Google Scholar 

  13. Scofeld, V.L. & Weissman, I.L. Allorecognition in biological systems. Dev. Comp. Immunol. 5, 23–28 (1981).

    Article  Google Scholar 

  14. De Tomaso, A.W. et al. Isolation and characterization of a protochordate histocompatibility locus. Nature 438, 454–459 (2005).

    Article  CAS  Google Scholar 

  15. Kärre, K. How to recognize a foreign submarine. Immunol. Rev. 155, 5–9 (1997).

    Article  Google Scholar 

  16. Kärre, K. On the Immunobiology of Natural Killer Cells. Doctoral thesis, Karolinska Institute (1981).

    Google Scholar 

  17. Kärre, K. Role of target histocompatibility antigens in regulation of natural killer activity: a reevaluation and a hypothesis. in Mechanisms of Cytotoxicity by NK Cells (eds. Callewaert, D. & Herberman, R.B.) 81–91 (Academic, San Diego, 1985).

    Chapter  Google Scholar 

  18. Ljunggren, H.G. & Kärre, K. In search of the 'missing self': MHC molecules and NK cell recognition. Immunol. Today 11, 237–241 (1990).

    Article  CAS  Google Scholar 

  19. Ljunggren, H.G. & Kärre, K. Host resistance directed selectively against H-2 deficient lymphoma variants. Analysis of the mechanism. J. Exp. Med. 162, 1745–1753 (1985).

    Article  CAS  Google Scholar 

  20. Kärre, K., Ljunggren, H.G., Piontek, G. & Kiessling, R. Selective rejection of H-2 deficient lymphoma variants suggests alternative immune defence strategy. Nature 319, 675–678 (1986).

    Article  Google Scholar 

  21. Piontek, G. et al. YAC-1 MHC class I variants reveal an association between decreased NK sensitivity and increased H-2 expression following IFN treatment or in vivo passage. J. Immunol. 135, 4281–4288 (1985).

    CAS  PubMed  Google Scholar 

  22. Taniguchi, K. et al. Interferon γ induces lung colonization by intravenously inoculated B 16 melanoma cells in parallel with enhanced expression of class I major histocompatibility complex antigens. Proc. Natl. Acad. Sci. USA 84, 3405–3409 (1987).

    Article  CAS  Google Scholar 

  23. Höglund, P. et al. Natural resistance against lymphoma grafts conveyed by H-2Dd transgene to C57Bl mice. J. Exp. Med. 168, 1469–1474 (1988).

    Article  Google Scholar 

  24. Öhlén, C. et al. Prevention of allogeneic bone marrow graft rejection by H-2 transgene in donor mice. Science 246, 666–668 (1989).

    Article  Google Scholar 

  25. Quillet, A. et al. Increased resistance to non-MHC-restricted cytotoxicity related to HLA-A, B expression. Direct demonstration using β2-microglobulin-transfected Daudi cells. J. Immunol. 141, 17–28 (1988).

    CAS  PubMed  Google Scholar 

  26. Storkus, W.J., Alexander, J., Payne, J.A., Dawson, J.R. & Cresswell, P. Reversal of natural killing susceptibility in target cells expressing transfected class I genes. Proc. Natl. Acad. Sci. USA 86, 2361–2364 (1989).

    Article  CAS  Google Scholar 

  27. Kärre, K. NK cells, MHC class I molecules and the missing self. Scand. J. Immunol. 55, 221–228 (2002).

    Article  Google Scholar 

  28. Kärre, K. MHC gene control of the natural killer system at the level of the target and the host. Semin. Cancer Biol. 2, 295–309 (1991).

    PubMed  Google Scholar 

Download references

Acknowledgements

My work has been supported by Karolinska Institute, the Swedish Cancer Society, the Swedish Research Council, the Swedish Foundation for Strategic Research, the Göran Gustafsson Foundation and the European Molecular Biology Organization. I thank all collaborators in the past and present: graduate students, undergraduate students, postdoctoral fellows, mentors and collaborators in other groups in many different countries, especially R. Kiessling, H.-G. Ljunggren, G. Klein, P. Höglund and C. Öhlén.

Author information

Authors and Affiliations

  1. Department of Microbiology, Klas Kärre is at the Strategic Research Center for Studies of Integrative Recognition in the Immune System (IRIS), Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. klas.karre@ki.se,

    Klas Kärre

Authors
  1. Klas Kärre
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kärre, K. Natural killer cell recognition of missing self. Nat Immunol 9, 477–480 (2008). https://doi.org/10.1038/ni0508-477

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni0508-477

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing