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. 1991 Aug 1;174(2):327–334. doi: 10.1084/jem.174.2.327

Alteration of the natural killer repertoire in H-2 transgenic mice: specificity of rapid lymphoma cell clearance determined by the H-2 phenotype of the target

PMCID: PMC2118914  PMID: 1856626

Abstract

The mechanism behind natural tumor resistance conveyed by a H-2Dd transgene to C57Bl/6 (B6) mice was investigated. Transgenic D8 mice were more efficient than control mice in natural killer (NK) cell mediated rapid elimination of intravenously inoculated radiolabeled lymphoma cells of B6 origin, such as RBL-5. There was no difference between D8 and B6 mice when elimination of YAC-1 targets was monitored. The effect of the transgene on the NK repertoire was related to the H-2 phenotype of the target: the differential elimination of RBL-5 lymphoma cells in D8 and B6 mice was not seen when a H-2 deficient variant of this line was used (efficiently eliminated in both genotypes), nor was it seen with a H-2Dd transfectant (surviving in both genotypes). The data show that a MHC class I transgene can directly control natural killing in vivo by altering the repertoire rather than the general levels of NK activity. Since the NK mediated elimination seen after introduction of a novel gene in the host was neutralized by introducing the same gene (H-2Dd), but not an unrelated class I gene (H-2Dp), in the tumor, the data support the concept of NK surveillance against missing self. This combined transgenic/transfectant system may serve as a tool for a molecular dissection of the interactions between NK cells and their targets in vivo.

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Selected References

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  1. Bennett M. Biology and genetics of hybrid resistance. Adv Immunol. 1987;41:333–445. doi: 10.1016/s0065-2776(08)60034-6. [DOI] [PubMed] [Google Scholar]
  2. Bieberich C., Scangos G., Tanaka K., Jay G. Regulated expression of a murine class I gene in transgenic mice. Mol Cell Biol. 1986 Apr;6(4):1339–1342. doi: 10.1128/mcb.6.4.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bieberich C., Yoshioka T., Tanaka K., Jay G., Scangos G. Functional expression of a heterologous major histocompatibility complex class I gene in transgenic mice. Mol Cell Biol. 1987 Nov;7(11):4003–4009. doi: 10.1128/mcb.7.11.4003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bix M., Liao N. S., Zijlstra M., Loring J., Jaenisch R., Raulet D. Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature. 1991 Jan 24;349(6307):329–331. doi: 10.1038/349329a0. [DOI] [PubMed] [Google Scholar]
  5. Carlson G. A., Melnychuk D., Meeker M. J. H-2 associated resistance to leukaemia transplantation: natural killing in vivo. Int J Cancer. 1980 Jan 15;25(1):111–122. doi: 10.1002/ijc.2910250115. [DOI] [PubMed] [Google Scholar]
  6. Carlson G. A., Wegmann T. G. Rapid in vivo destruction of semi-syngeneic and allogeneic cells by nonimmunized mice as a consequence of nonidentity at H-2. J Immunol. 1977 Jun;118(6):2130–2137. [PubMed] [Google Scholar]
  7. Ciccone E., Pende D., Viale O., Tambussi G., Ferrini S., Biassoni R., Longo A., Guardiola J., Moretta A., Moretta L. Specific recognition of human CD3-CD16+ natural killer cells requires the expression of an autosomic recessive gene on target cells. J Exp Med. 1990 Jul 1;172(1):47–52. doi: 10.1084/jem.172.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cudkowicz G., Bennett M. Peculiar immunobiology of bone marrow allografts. II. Rejection of parental grafts by resistant F 1 hybrid mice. J Exp Med. 1971 Dec 1;134(6):1513–1528. doi: 10.1084/jem.134.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Evans G. A., Margulies D. H., Shykind B., Seidman J. G., Ozato K. Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens. Nature. 1982 Dec 23;300(5894):755–757. doi: 10.1038/300755a0. [DOI] [PubMed] [Google Scholar]
  10. Harmon R. C., Stein N., Frelinger J. A. Monoclonal antibodies reactive with H-2 determinants. Immunogenetics. 1983;18(5):541–545. doi: 10.1007/BF00364395. [DOI] [PubMed] [Google Scholar]
  11. Heslop B. F., McNeilage L. J. The F1 hybrid effect in allogeneic lymphocyte cytotoxicity. Points of similarity between hybrid resistance and ALC. Transplantation. 1989 Oct;48(4):634–639. [PubMed] [Google Scholar]
  12. Höglund P., Ljunggren H. G., Ohlén C., Ahrlund-Richter L., Scangos G., Bieberich C., Jay G., Klein G., Kärre K. Natural resistance against lymphoma grafts conveyed by H-2Dd transgene to C57BL mice. J Exp Med. 1988 Oct 1;168(4):1469–1474. doi: 10.1084/jem.168.4.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koo G. C., Peppard J. R. Establishment of monoclonal anti-Nk-1.1 antibody. Hybridoma. 1984 Fall;3(3):301–303. doi: 10.1089/hyb.1984.3.301. [DOI] [PubMed] [Google Scholar]
  14. Kärre K., Klein G. O., Kiessling R., Klein G., Roder J. C. In vitro NK-activity and in vivo resistance to leukemia: studies of beige, beige//nude and wild-type hosts on C57BL background. Int J Cancer. 1980 Dec 15;26(6):789–797. doi: 10.1002/ijc.2910260613. [DOI] [PubMed] [Google Scholar]
  15. Kärre K., Ljunggren H. G., Piontek G., Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986 Feb 20;319(6055):675–678. doi: 10.1038/319675a0. [DOI] [PubMed] [Google Scholar]
  16. Lanzavecchia A. Receptor-mediated antigen uptake and its effect on antigen presentation to class II-restricted T lymphocytes. Annu Rev Immunol. 1990;8:773–793. doi: 10.1146/annurev.iy.08.040190.004013. [DOI] [PubMed] [Google Scholar]
  17. Levitsky H. I., Golumbek P. T., Pardoll D. M. The fate of CD4-8- T cell receptor-alpha beta+ thymocytes. J Immunol. 1991 Feb 15;146(4):1113–1117. [PubMed] [Google Scholar]
  18. Ljunggren H. G., Kärre K. Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism. J Exp Med. 1985 Dec 1;162(6):1745–1759. doi: 10.1084/jem.162.6.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ljunggren H. G., Kärre K. In search of the 'missing self': MHC molecules and NK cell recognition. Immunol Today. 1990 Jul;11(7):237–244. doi: 10.1016/0167-5699(90)90097-s. [DOI] [PubMed] [Google Scholar]
  20. Ljunggren H. G., Ohlén C., Höglund P., Yamasaki T., Klein G., Kärre K. Afferent and efferent cellular interactions in natural resistance directed against MHC class I deficient tumor grafts. J Immunol. 1988 Jan 15;140(2):671–678. [PubMed] [Google Scholar]
  21. Ljunggren H. G., Päbo S., Cochet M., Kling G., Kourilsky P., Kärre K. Molecular analysis of H-2-deficient lymphoma lines. Distinct defects in biosynthesis and association of MHC class I heavy chains and beta 2-microglobulin observed in cells with increased sensitivity to NK cell lysis. J Immunol. 1989 Apr 15;142(8):2911–2917. [PubMed] [Google Scholar]
  22. Macchi M. J., Woodward J. G., McLaughlin-Taylor E., Griffin J., Hood L., Frelinger J. A. Cloning and identification of the H-2Dp gene. Immunogenetics. 1984;19(3):195–204. doi: 10.1007/BF00364763. [DOI] [PubMed] [Google Scholar]
  23. Ohlén C., Kling G., Höglund P., Hansson M., Scangos G., Bieberich C., Jay G., Kärre K. Prevention of allogeneic bone marrow graft rejection by H-2 transgene in donor mice. Science. 1989 Nov 3;246(4930):666–668. doi: 10.1126/science.2814488. [DOI] [PubMed] [Google Scholar]
  24. Ozato K., Mayer N. M., Sachs D. H. Monoclonal antibodies to mouse major histocompatibility complex antigens. Transplantation. 1982 Sep;34(3):113–120. doi: 10.1097/00007890-198209000-00001. [DOI] [PubMed] [Google Scholar]
  25. Riccardi C., Santoni A., Barlozzari T., Puccetti P., Herberman R. B. In vivo natural reactivity of mice against tumor cells. Int J Cancer. 1980 Apr 15;25(4):475–486. doi: 10.1002/ijc.2910250409. [DOI] [PubMed] [Google Scholar]
  26. Rolstad B., Fossum S. Allogeneic lymphocyte cytotoxicity (ALC) in rats: establishment of an in vitro assay, and direct evidence that cells with natural killer (NK) activity are involved in ALC. Immunology. 1987 Feb;60(2):151–157. [PMC free article] [PubMed] [Google Scholar]
  27. SNELL G. D., STEVENS L. C. Histocompatibility genes of mice. III. H-1 and H-4, two histocompatibility loci in the first linkage group. Immunology. 1961 Oct;4:366–379. [PMC free article] [PubMed] [Google Scholar]
  28. Seaman W. E., Sleisenger M., Eriksson E., Koo G. C. Depletion of natural killer cells in mice by monoclonal antibody to NK-1.1. Reduction in host defense against malignancy without loss of cellular or humoral immunity. J Immunol. 1987 Jun 15;138(12):4539–4544. [PubMed] [Google Scholar]
  29. Snell G. D. Recognition structures determined by the H-2 complex. Transplant Proc. 1976 Jun;8(2):147–156. [PubMed] [Google Scholar]
  30. Stein-Streilein J., Bennett M., Mann D., Kumar V. Natural killer cells in mouse lung: surface phenotype, target preference, and response to local influenza virus infection. J Immunol. 1983 Dec;131(6):2699–2704. [PubMed] [Google Scholar]
  31. Storkus W. J., Alexander J., Payne J. A., Cresswell P., Dawson J. R. The alpha 1/alpha 2 domains of class I HLA molecules confer resistance to natural killing. J Immunol. 1989 Dec 1;143(11):3853–3857. [PubMed] [Google Scholar]
  32. Townsend A., Bodmer H. Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol. 1989;7:601–624. doi: 10.1146/annurev.iy.07.040189.003125. [DOI] [PubMed] [Google Scholar]
  33. Yankelevich B., Knobloch C., Nowicki M., Dennert G. A novel cell type responsible for marrow graft rejection in mice. T cells with NK phenotype cause acute rejection of marrow grafts. J Immunol. 1989 May 15;142(10):3423–3430. [PubMed] [Google Scholar]
  34. Yoshioka T., Bieberich C., Scangos G., Jay G. A transgenic class I antigen is recognized as self and functions as a restriction element. J Immunol. 1987 Dec 1;139(11):3861–3867. [PubMed] [Google Scholar]

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