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.

Selective rejection of H–2-deficient lymphoma variants suggests alternative immune defence strategy

Abstract

Metazoan organisms may discriminate between self and non-self not only by the presence of foreign antigens but also by the absence of normal self markers1. Mammalian adaptive immune responses use the first strategy, with the additional requirement that foreign antigens are recognized in the context of self-major histocompatibility complex (MHC) products at the cell surface2. Aberrant cells which fail to express MHC products adequately can therefore avoid detection2–4. A more primitive but complementary defence system, eliminating such cells on the basis of absent self-markers, is suggested by a re-interpretation5,6 of phenomena associated with metastasis and natural resistance. We now show that murine lymphoma cells selected for loss of H–2 expression are less malignant after low-dose inoculation in syngeneic hosts than are wild-type cells, and that the rejection of such cells is non-adaptive. On the basis of our data, we suggest that natural killer cells are effector cells in a defence system geared to detect the deleted or reduced expression of self-MHC.

References

  1. 1

    Burnet, F. M. Nature 232, 230–235 (1971).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Zinkernagel, R. M. & Doherty, P. C. J. exp. Med. 141, 1427–1436 (1975).

    CAS  Article  Google Scholar 

  3. 3

    Doherty, P. C., Knowles, B. B. & Wettstein, P. J. Adv. Cancer Res. 42, 1–66 (1984).

    CAS  Article  Google Scholar 

  4. 4

    Sanderson, A. R. & Beverley, P. C. L. Immun. Today 4, 211–213 (1983).

    CAS  Article  Google Scholar 

  5. 5

    Kärre, K. thesis, Karolinska Inst. (1981).

  6. 6

    Kärre, K. in Mechanisms of Cytoxicity by Natural Killer Cells (eds Herberman, R. B. & Callewaert, D.) 81–91 (Academic, Orlando, 1985).

    Google Scholar 

  7. 7

    Kärre, K., Klein, G. O., Kiessling, R., Klein, G. & Roder, J. C. Int. J. Cancer 26, 789–797 (1980).

    Article  Google Scholar 

  8. 8

    Klein, J. in Biology of the Mouse Histocompatibility-2 Complex, 36–37 (Springer, New York, 1975).

    Google Scholar 

  9. 9

    Boon, R., Adv. Cancer Res. 39, 121–151 (1983).

    CAS  Article  Google Scholar 

  10. 10

    Frost, P., Kerbel, R. S., Bauer, E., Tartanella-Biondo, R. & Cefalu, W. Cancer Res. 43, 125–132 (1983).

    CAS  PubMed  Google Scholar 

  11. 11

    Hui, K., Grosvels, F. & Festenstein, H. Nature 311, 750–752 (1984).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Hämmerling, G. J. et al. Nature 315, 301–306 (1985).

    ADS  Article  Google Scholar 

  13. 13

    Bevan, M. J. J. exp. Med. 142, 1349–1364 (1975).

    CAS  Article  Google Scholar 

  14. 14

    Cudkowicz, G. & Hochman, P. S. Immun. Rev. 44, 13–41 (1979).

    CAS  Article  Google Scholar 

  15. 15

    Cikes, M., Friberg, S. Jr & Klein, G. J. natn. Cancer Inst. 30, 347–361 (1973).

    Article  Google Scholar 

  16. 16

    Stern, P. et al. Nature 285, 341–342 (1982).

    ADS  Article  Google Scholar 

  17. 17

    Hansson, M. et al. J. Immun. 123, 765–771 (1979).

    CAS  PubMed  Google Scholar 

  18. 18

    Carlson, G. A., Melnychuk, D. & Meeker, M. J. Int. J. Cancer 25, 111–122 (1980).

    CAS  Article  Google Scholar 

  19. 19

    Hansson, M., Kiessling, R., Andersson, B. & Welsh, R. M. J. Immun. 125, 2225–2231 (1980).

    CAS  PubMed  Google Scholar 

  20. 20

    Becker, S., Kiessling, R., Lee, N. & Klein, G. J. natn. Cancer Inst. 61, 1493–1498 (1978).

    Google Scholar 

  21. 21

    Cudkowicz, G. & Bennet, M. J. exp. Med. 134, 1513–1528 (1971).

    CAS  Article  Google Scholar 

  22. 22

    Klein, G. O., Klein, G., Kiessling, R. & Kärre, K. Immunogenetics 6, 561–569 (1978).

    Article  Google Scholar 

  23. 23

    Rolstad, B. & Ford, W. L. Immun. Rev. 73, 87–114 (1983).

    CAS  Article  Google Scholar 

  24. 24

    Möller, E. J. natn. Cancer Inst. 33, 979–987 (1964).

    Google Scholar 

  25. 25

    Haywood, G. R. & McKhann, C. J. exp. Med. 133, 1171–1187 (1971).

    CAS  Article  Google Scholar 

  26. 26

    Katzav, S., De Baetselier, P., Tarbakovsky, B., Feldman, M. & Segal, S. J. natn. Cancer Inst. 71, 317–324 (1983).

    CAS  Google Scholar 

  27. 27

    Eisenbach, L., Segal, S. & Feldman, M. Int. J. Cancer 32, 113–120 (1983).

    CAS  Article  Google Scholar 

  28. 28

    Gooding, L. R. J. Immun. 129, 1306–1312 (1982).

    CAS  Google Scholar 

  29. 29

    Schrier, P. I., Bernards, R., Vaessen, J., Houweling, A. & van der Eb, A. J. Nature 305, 771–775 (1983).

    ADS  CAS  Article  Google Scholar 

  30. 30

    Gidlund, M. et al. Nature 292, 848–850 (1981).

    ADS  CAS  Article  Google Scholar 

  31. 31

    Scofield, V. L., Schlumpberger, J. M., West, L. A. & Weissman, I. L. Nature 295, 499–502 (1982).

    ADS  CAS  Article  Google Scholar 

  32. 32

    Hecht, T. & Summers, D. J. Virol. 10, 378–385 (1972).

    Google Scholar 

  33. 33

    Welsh, R.M., Kärre, K., Hansson, M., Kunkel, L.A. & Kiessling, R. J. Immun. 126, 219–225 (1981).

    CAS  PubMed  Google Scholar 

  34. 34

    Snell, G. Transplantn Proc. 8, 147–156 (1976).

    CAS  Google Scholar 

  35. 35

    Dausset, J. Devl comp. Immun. 5, 1–4 (1981).

    CAS  Article  Google Scholar 

  36. 36

    Brickell, P. M., Latchman, D., Murphy, D., Wilson, K. & Rigby, P. W. J. Nature 306, 756–761 (1984).

    ADS  CAS  Article  Google Scholar 

  37. 37

    Baldacci, P., Pozo, F., Gisselbrecht, S. & Kourilsky, P. J. exp. Med. 158, 1294–1306 (1981).

    Article  Google Scholar 

  38. 38

    Ozato, K. & Sachs, D. H. J. Immun. 126, 317–321 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Kärre, K., Seeley, J., Eriksson, E., Burton, R. & Kiessling, R. J. exp. Med. 156, 385–403 (1983).

    Article  Google Scholar 

  40. 40

    Julius, M. H., Simpson, E. & Herzenberg, L. A. Eur. J. Immun. 3, 645–651 (1973).

    CAS  Article  Google Scholar 

  41. 41

    Piontek, G. et al. J. Immun. 135, 4281–4288 (1985).

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kärre, K., Ljunggren, H., Piontek, G. et al. Selective rejection of H–2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319, 675–678 (1986). https://doi.org/10.1038/319675a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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