Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1987 Nov;7(11):4003–4009. doi: 10.1128/mcb.7.11.4003

Functional expression of a heterologous major histocompatibility complex class I gene in transgenic mice.

C Bieberich 1, T Yoshioka 1, K Tanaka 1, G Jay 1, G Scangos 1
PMCID: PMC368069  PMID: 3323884

Abstract

The regulated expression of major histocompatibility complex class I antigens is essential for assuring proper cellular immune responses. To study H-2 class I gene regulation, we have transferred a foreign class I gene to inbred mice and have previously shown that the heterologous class I gene was expressed in a tissue-dependent manner. In this report, we demonstrate that these mice expressed the transgenic class I molecule on the cell surface without any alteration in the level of endogenous H-2 class I antigens. Skin grafts from transgenic mice were rapidly rejected by mice of the background strain, indicating that the transgenic antigen was expressed in an immunologically functional form. As with endogenous H-2 class I genes, the class I transgene was inducible by interferon treatment and suppressible by human adenovirus 12 transformation. Linkage analysis indicated that the transgene was not closely linked to endogenous class I loci, suggesting that trans-regulation of class I genes can occur for class I genes located outside the major histocompatibility complex.

Full text

PDF
4003

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernards R., Dessain S. K., Weinberg R. A. N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma. Cell. 1986 Dec 5;47(5):667–674. doi: 10.1016/0092-8674(86)90509-x. [DOI] [PubMed] [Google Scholar]
  2. Bernards R., Houweling A., Schrier P. I., Bos J. L., Van der Eb A. J. Characterization of cells transformed by Ad5/Ad12 hybrid early region I plasmids. Virology. 1982 Jul 30;120(2):422–432. doi: 10.1016/0042-6822(82)90042-3. [DOI] [PubMed] [Google Scholar]
  3. Bernards R., Schrier P. I., Houweling A., Bos J. L., van der Eb A. J., Zijlstra M., Melief C. J. Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. 1983 Oct 27-Nov 2Nature. 305(5937):776–779. doi: 10.1038/305776a0. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Burrone O. R., Milstein C. Control of HLA-A,B,C synthesis and expression in interferon-treated cells. EMBO J. 1982;1(3):345–349. doi: 10.1002/j.1460-2075.1982.tb01172.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Collins T., Lapierre L. A., Fiers W., Strominger J. L., Pober J. S. Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A,B antigens in vascular endothelial cells and dermal fibroblasts in vitro. Proc Natl Acad Sci U S A. 1986 Jan;83(2):446–450. doi: 10.1073/pnas.83.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fellous M., Nir U., Wallach D., Merlin G., Rubinstein M., Revel M. Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells. Proc Natl Acad Sci U S A. 1982 May;79(10):3082–3086. doi: 10.1073/pnas.79.10.3082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Friedman R. L., Manly S. P., McMahon M., Kerr I. M., Stark G. R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984 Oct;38(3):745–755. doi: 10.1016/0092-8674(84)90270-8. [DOI] [PubMed] [Google Scholar]
  10. Goodenow R. S., Stroynowski I., McMillan M., Nicolson M., Eakle K., Sher B. T., Davidson N., Hood L. Expression of complete transplantation antigens by mammalian cells transformed with truncated class I genes. Nature. 1983 Feb 3;301(5899):388–394. doi: 10.1038/301388a0. [DOI] [PubMed] [Google Scholar]
  11. Huttner K. M., Scangos G. A., Ruddle F. H. DNA-mediated gene transfer of a circular plasmid into murine cells. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5820–5824. doi: 10.1073/pnas.76.11.5820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Israel A., Kimura A., Fournier A., Fellous M., Kourilsky P. Interferon response sequence potentiates activity of an enhancer in the promoter region of a mouse H-2 gene. Nature. 1986 Aug 21;322(6081):743–746. doi: 10.1038/322743a0. [DOI] [PubMed] [Google Scholar]
  13. Kimura A., Israël A., Le Bail O., Kourilsky P. Detailed analysis of the mouse H-2Kb promoter: enhancer-like sequences and their role in the regulation of class I gene expression. Cell. 1986 Jan 31;44(2):261–272. doi: 10.1016/0092-8674(86)90760-9. [DOI] [PubMed] [Google Scholar]
  14. Kobori J. A., Strauss E., Minard K., Hood L. Molecular analysis of the hotspot of recombination in the murine major histocompatibility complex. Science. 1986 Oct 10;234(4773):173–179. doi: 10.1126/science.3018929. [DOI] [PubMed] [Google Scholar]
  15. Kress M., Barra Y., Seidman J. G., Khoury G., Jay G. Functional insertion of an Alu type 2 (B2 SINE) repetitive sequence in murine class I genes. Science. 1984 Nov 23;226(4677):974–977. doi: 10.1126/science.6095445. [DOI] [PubMed] [Google Scholar]
  16. Kress M., Liu W. Y., Jay E., Khoury G., Jay G. Comparison of class I (H-2) gene sequences. Derivation of unique probes for members of this multigene family. J Biol Chem. 1983 Nov 25;258(22):13929–13936. [PubMed] [Google Scholar]
  17. Lindahl P., Gresser I., Leary P., Tovey M. Interferon treatment of mice: enhanced expression of histocompatibility antigens on lymphoid cells. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1284–1287. doi: 10.1073/pnas.73.4.1284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. May L. T., Helfgott D. C., Sehgal P. B. Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the beta 2 interferon involved. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8957–8961. doi: 10.1073/pnas.83.23.8957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Meruelo D., Kornreich R., Rossomando A., Pampeno C., Boral A., Silver J. L., Buxbaum J., Weiss E. H., Devlin J. J., Mellor A. L. Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4504–4508. doi: 10.1073/pnas.83.12.4504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ozato K., Hansen T. H., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. II. Antibodies to the H-2Ld antigen, the products of a third polymorphic locus of the mouse major histocompatibility complex. J Immunol. 1980 Dec;125(6):2473–2477. [PubMed] [Google Scholar]
  21. 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]
  22. Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
  23. Rosa F., Le Bouteiller P. P., Abadie A., Mishal Z., Lemonnier F. A., Bourrel D., Lamotte M., Kalil J., Jordan B., Fellous M. HLA class I genes integrated into murine cells are inducible by interferon. Eur J Immunol. 1983 Jun;13(6):495–499. doi: 10.1002/eji.1830130612. [DOI] [PubMed] [Google Scholar]
  24. Rosenberg A. S., Mizuochi T., Singer A. Analysis of T-cell subsets in rejection of Kb mutant skin allografts differing at class I MHC. 1986 Aug 28-Sep 3Nature. 322(6082):829–831. doi: 10.1038/322829a0. [DOI] [PubMed] [Google Scholar]
  25. Schmidt W., Alonso A., Leben L., Festenstein H. Differential regulation of H-2 antigen expression in tumors and its biologic consequences. Transplant Proc. 1981 Dec;13(4):1814–1818. [PubMed] [Google Scholar]
  26. Schrier P. I., Bernards R., Vaessen R. T., Houweling A., van der Eb A. J. Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. 1983 Oct 27-Nov 2Nature. 305(5937):771–775. doi: 10.1038/305771a0. [DOI] [PubMed] [Google Scholar]
  27. Small J. A., Blair D. G., Showalter S. D., Scangos G. A. Analysis of a transgenic mouse containing simian virus 40 and v-myc sequences. Mol Cell Biol. 1985 Apr;5(4):642–648. doi: 10.1128/mcb.5.4.642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smithies O., Gregg R. G., Boggs S. S., Koralewski M. A., Kucherlapati R. S. Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination. Nature. 1985 Sep 19;317(6034):230–234. doi: 10.1038/317230a0. [DOI] [PubMed] [Google Scholar]
  29. Tanaka K., Appella E., Jay G. Developmental activation of the H-2K gene is correlated with an increase in DNA methylation. Cell. 1983 Dec;35(2 Pt 1):457–465. doi: 10.1016/0092-8674(83)90179-4. [DOI] [PubMed] [Google Scholar]
  30. Tanaka K., Hayashi H., Hamada C., Khoury G., Jay G. Expression of major histocompatibility complex class I antigens as a strategy for the potentiation of immune recognition of tumor cells. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8723–8727. doi: 10.1073/pnas.83.22.8723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tanaka K., Isselbacher K. J., Khoury G., Jay G. Reversal of oncogenesis by the expression of a major histocompatibility complex class I gene. Science. 1985 Apr 5;228(4695):26–30. doi: 10.1126/science.3975631. [DOI] [PubMed] [Google Scholar]
  32. Thomas K. R., Capecchi M. R. Introduction of homologous DNA sequences into mammalian cells induces mutations in the cognate gene. Nature. 1986 Nov 6;324(6092):34–38. doi: 10.1038/324034a0. [DOI] [PubMed] [Google Scholar]
  33. Vogel J., Kress M., Khoury G., Jay G. A transcriptional enhancer and an interferon-responsive sequence in major histocompatibility complex class I genes. Mol Cell Biol. 1986 Oct;6(10):3550–3554. doi: 10.1128/mcb.6.10.3550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yoshie O., Schmidt H., Lengyel P., Reddy E. S., Morgan W. R., Weissman S. M. Transcripts of human HLA gene fragments lacking the 5'-terminal region in transfected mouse cells. Proc Natl Acad Sci U S A. 1984 Feb;81(3):649–653. doi: 10.1073/pnas.81.3.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES