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. 1991 Feb;72(2):277–281.

Reduced stimulation of helper T cells by Ki-ras transformed cells.

D J Maudsley 1, W J Bateman 1, A G Morris 1
PMCID: PMC1384496  PMID: 1826672

Abstract

A number of viral genes and cellular oncogenes inhibit major histocompatibility complex (MHC) antigen expression at the cell surface. In the case of inhibition of class I MHC antigens by viral genes this results in a reduced recognition by antigen-specific cytotoxic T cells. The activated Ki-ras cellular oncogene carried by the Ki-murine sarcoma virus (Ki-MuSV) in contrast inhibits class II MHC (or Ia) antigen expression on transformed cells. We have studied how transformation with Ki-ras affects recognition by alloreactive helper T cells. We found that the Ki-ras inhibition of class II MHC antigen expression led to greatly reduced stimulation of alloreactive T cells to proliferate and to secrete interferon-gamma (IFN-gamma). These findings support our hypothesis that the ability of an oncogene to reduce class II MHC antigen expression is crucial to its ability to produce tumour cells.

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Selected References

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  1. Andersson M., McMichael A., Peterson P. A. Reduced allorecognition of adenovirus-2 infected cells. J Immunol. 1987 Jun 1;138(11):3960–3966. [PubMed] [Google Scholar]
  2. Atkins G. J., Johnston M. D., Westmacott L. M., Burke D. C. Department of Biological Sciences, University of Warwick, Coventry, CV47AL, England. J Gen Virol. 1974 Dec;25(3):381–390. doi: 10.1099/0022-1317-25-3-381. [DOI] [PubMed] [Google Scholar]
  3. Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
  4. Bateman W. J., Jenkinson E. J., Owen J. J. T-cell immunity to murine Moloney sarcoma virus-induced tumours: L3T4+ T cells are necessary for resistance to primary sarcoma growth, but Lyt-2+ T cells are required for resistance to secondary tumour cell challenge. Immunology. 1987 Jul;61(3):317–320. [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Bos J. L., Fearon E. R., Hamilton S. R., Verlaan-de Vries M., van Boom J. H., van der Eb A. J., Vogelstein B. Prevalence of ras gene mutations in human colorectal cancers. 1987 May 28-Jun 3Nature. 327(6120):293–297. doi: 10.1038/327293a0. [DOI] [PubMed] [Google Scholar]
  8. Cher D. J., Mosmann T. R. Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. J Immunol. 1987 Jun 1;138(11):3688–3694. [PubMed] [Google Scholar]
  9. Cresswell P. Immunology: questions of presentation. Nature. 1990 Feb 15;343(6259):593–594. doi: 10.1038/343593a0. [DOI] [PubMed] [Google Scholar]
  10. Fong T. A., Mosmann T. R. The role of IFN-gamma in delayed-type hypersensitivity mediated by Th1 clones. J Immunol. 1989 Nov 1;143(9):2887–2893. [PubMed] [Google Scholar]
  11. Forrester K., Almoguera C., Han K., Grizzle W. E., Perucho M. Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. 1987 May 28-Jun 3Nature. 327(6120):298–303. doi: 10.1038/327298a0. [DOI] [PubMed] [Google Scholar]
  12. Geppert T. D., Lipsky P. E. Dissection of defective antigen presentation by interferon-gamma-treated fibroblasts. J Immunol. 1987 Jan 15;138(2):385–392. [PubMed] [Google Scholar]
  13. Germain R. N. Immunology. The ins and outs of antigen processing and presentation. Nature. 1986 Aug 21;322(6081):687–689. doi: 10.1038/322687a0. [DOI] [PubMed] [Google Scholar]
  14. Harding C. V., Unanue E. R. Quantitation of antigen-presenting cell MHC class II/peptide complexes necessary for T-cell stimulation. Nature. 1990 Aug 9;346(6284):574–576. doi: 10.1038/346574a0. [DOI] [PubMed] [Google Scholar]
  15. Hämmerling G. J., Klar D., Pülm W., Momburg F., Moldenhauer G. The influence of major histocompatibility complex class I antigens on tumor growth and metastasis. Biochim Biophys Acta. 1987 Nov 25;907(3):245–259. doi: 10.1016/0304-419x(87)90008-4. [DOI] [PubMed] [Google Scholar]
  16. Lechler R. I., Norcross M. A., Germain R. N. Qualitative and quantitative studies of antigen-presenting cell function by using I-A-expressing L cells. J Immunol. 1985 Nov;135(5):2914–2922. [PubMed] [Google Scholar]
  17. Margulies D. H. Immunology. Naked or peptide-clothed MHC? Nature. 1989 Nov 9;342(6246):124–125. doi: 10.1038/342124a0. [DOI] [PubMed] [Google Scholar]
  18. Matis L. A., Glimcher L. H., Paul W. E., Schwartz R. H. Magnitude of response of histocompatibility-restricted T-cell clones is a function of the product of the concentrations of antigen and Ia molecules. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6019–6023. doi: 10.1073/pnas.80.19.6019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Maudsley D. J., Morris A. G. Kirsten murine sarcoma virus abolishes interferon gamma-induced class II but not class I major histocompatibility antigen expression in a murine fibroblast line. J Exp Med. 1988 Feb 1;167(2):706–711. doi: 10.1084/jem.167.2.706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Maudsley D. J., Morris A. G. Regulation of IFN-gamma-induced host cell MHC antigen expression by Kirsten MSV and MLV. I. Effects on class I antigen expression. Immunology. 1989 May;67(1):21–25. [PMC free article] [PubMed] [Google Scholar]
  21. Maudsley D. J., Morris A. G. Regulation of IFN-gamma-induced host cell MHC antigen expression by Kirsten MSV and MLV. II. Effects on class II antigen expression. Immunology. 1989 May;67(1):26–31. [PMC free article] [PubMed] [Google Scholar]
  22. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  23. Norton J. D., Connor J., Avery R. J. Genesis of Kirsten murine sarcoma virus: sequence analysis reveals recombination points and potential leukaemogenic determinant on parental leukaemia virus genome. Nucleic Acids Res. 1984 Sep 11;12(17):6839–6852. doi: 10.1093/nar/12.17.6839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Powell P. C., Hála K., Wick G. Aberrant expression of Ia-like antigens on tumor cells of regressing but not of progressing Rous sarcomas. Eur J Immunol. 1987 May;17(5):723–726. doi: 10.1002/eji.1830170523. [DOI] [PubMed] [Google Scholar]
  25. Prat M., Bretti S., Amedeo M., Landolfo S., Comoglio P. M. Monoclonal antibodies against murine IFN-gamma abrogate in vivo tumor immunity against RSV-induced murine sarcomas. J Immunol. 1987 Jun 15;138(12):4530–4533. [PubMed] [Google Scholar]
  26. Reznikoff C. A., Brankow D. W., Heidelberger C. Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res. 1973 Dec;33(12):3231–3238. [PubMed] [Google Scholar]
  27. Schwartz R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol. 1985;3:237–261. doi: 10.1146/annurev.iy.03.040185.001321. [DOI] [PubMed] [Google Scholar]
  28. Smith M. E., Bodmer J. G., Kelly A. P., Trowsdale J., Kirkland S. C., Bodmer W. F. Variation in HLA expression on tumors: an escape from immune response. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):581–586. doi: 10.1101/sqb.1989.054.01.069. [DOI] [PubMed] [Google Scholar]
  29. Tanaka K., Yoshioka T., Bieberich C., Jay G. Role of the major histocompatibility complex class I antigens in tumor growth and metastasis. Annu Rev Immunol. 1988;6:359–380. doi: 10.1146/annurev.iy.06.040188.002043. [DOI] [PubMed] [Google Scholar]
  30. Tomkins P. T., Ward G. A., Morris A. G. Role of interferon-gamma in T-cell responses to Semliki Forest virus-infected murine brain cells. Immunology. 1988 Mar;63(3):355–362. [PMC free article] [PubMed] [Google Scholar]
  31. Versteeg R., Krüse-Wolters K. M., Plomp A. C., van Leeuwen A., Stam N. J., Ploegh H. L., Ruiter D. J., Schrier P. I. Suppression of class I human histocompatibility leukocyte antigen by c-myc is locus specific. J Exp Med. 1989 Sep 1;170(3):621–635. doi: 10.1084/jem.170.3.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Versteeg R., Noordermeer I. A., Krüse-Wolters M., Ruiter D. J., Schrier P. I. c-myc down-regulates class I HLA expression in human melanomas. EMBO J. 1988 Apr;7(4):1023–1029. doi: 10.1002/j.1460-2075.1988.tb02909.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vignaux F., Gresser I. Differential effects of interferon on the expression of H-2K, H-2D, and Ia antigens on mouse lymphocytes. J Immunol. 1977 Feb;118(2):721–723. [PubMed] [Google Scholar]
  34. Wedgwood J. F., Hatam L., Bonagura V. R. Effect of interferon-gamma and tumor necrosis factor on the expression of class I and class II major histocompatibility molecules by cultured human umbilical vein endothelial cells. Cell Immunol. 1988 Jan;111(1):1–9. doi: 10.1016/0008-8749(88)90046-9. [DOI] [PubMed] [Google Scholar]
  35. Wong G. H., Bartlett P. F., Clark-Lewis I., Battye F., Schrader J. W. Inducible expression of H-2 and Ia antigens on brain cells. Nature. 1984 Aug 23;310(5979):688–691. doi: 10.1038/310688a0. [DOI] [PubMed] [Google Scholar]
  36. Yewdell J. W., Bennink J. R., Eager K. B., Ricciardi R. P. CTL recognition of adenovirus-transformed cells infected with influenza virus: lysis by anti-influenza CTL parallels adenovirus-12-induced suppression of class I MHC molecules. Virology. 1988 Jan;162(1):236–238. doi: 10.1016/0042-6822(88)90413-8. [DOI] [PubMed] [Google Scholar]
  37. Zlotnik A., Shimonkevitz R. P., Gefter M. L., Kappler J., Marrack P. Characterization of the gamma-interferon-mediated induction of antigen-presenting ability in P388D1 cells. J Immunol. 1983 Dec;131(6):2814–2820. [PubMed] [Google Scholar]

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