Skip to main content

The loss of class II MHC antigen expression byras-transformed murine fibroblasts passaged as tumours correlates with increased tumorigenicity but is not mediated by T cells

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.


In several murine tumour systems, expression of class II major histocompatibility complex (MHC) antigens by tumour cells, either constitutive or inducible, correlates with reduced tumorigenicity as compared with equivalent class-II-negative cells, and CD4 phenotype T cells together with interferon γ (which induces the expression of class II) may be involved in the control of the proliferation of class-II-expressing tumours. This implies a potential T-cell-mediated selection pressure against class II expression. To test this possibility, we have repeatedly passaged as tumours in euthymic, syngeneic miceras-transformed murine fibroblast lines, which are class-II-inducible, to determine whether class-II-non-inducible variants are selected. We examined the expression of both class I and class II antigen in tumour cells re-established in vitro. It was found that the inducibility of class II, but not class I, expression rapidly diminished, correlating with augmented tumorigenicity. However, this loss of class II inducibility occurred in athymic as well as euthymic mice. Therefore, despite the fact that the tumorigenicity of these lines is augmented in euthymic mice depleted of CD4 T cells or interferon γ, we found no evidence of T-cell-mediated selection against class II expression. The loss of class II expression observed must be due to mechanisms other than immune selection. The possibility that this might result from other soluble factors modulating the response to interferon γ in vivo is discussed.

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


  1. 1.

    Bateman W, Jenkinson E, Owen J (1987) T-cell immunity to murine Moloney sarcoma virus-induced tumours: L3T4+ T cells are necessary for resistance to primary sarcoma growth, but Lyt-2+ cells are required for resistance to secondary tumour cell challenge. Immunology 61: 317

    Google Scholar 

  2. 2.

    Bateman WJ, Fiera R, Matthews N, Morris A (1990) Inducibility of class II major histocompatability antigens by interferon gamma is associated with reduced tumorigenicity in C3H mouse fibroblasts transformed by v-Ki-ras. J Exp Med 173: 193

    Google Scholar 

  3. 3.

    Bernards R, Schrier P, Houweling A, Bos J, van der Eb A, Zijlstra M, Melief C (1983) Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. Nature 305: 776

    Google Scholar 

  4. 4.

    Cobbold S, Jayasuriya A, Nash A, Prospero T, Waldman H (1984) Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature 312: 548

    Google Scholar 

  5. 5.

    Czarniecki C, Chiu H, Wong G, McCabe S, Palladino M (1988) Transforming growth factor β1 alters the expression of class II histocompatability antigens on human cells. J Immunol 12: 4212

    Google Scholar 

  6. 6.

    Dialynas D, Wilde D, Marrack P, Pierres A, Wall K, Havran W, Olten G, Loken M, Pierres M, Kappler J, Fitch F (1983) Characterisation of the murine antigen determinant, designated L3T4a, recognized by mab GK1.5: expression of L3T4a by functional T cell clones correlates with class II MHC antigen reactivity. Immunol Rev 74: 29

    Google Scholar 

  7. 7.

    Esteban F, Ruizcabello F, Concha A, Perezayala M, Sanchezrosas J, Garrido F (1990) HLA-Dr expression is associated with excellent prognosis in squamous cell carcinoma of the larynx. Clin Exp Metastasis 8: 319

    Google Scholar 

  8. 8.

    Feldmann M (1989), Molecular mechanisms involved in human autoimmune diseases: relevance of chronic antigen presentation, class II expression and cytokine production. Immunology [Suppl] 2: 66

    Google Scholar 

  9. 9.

    Greenberg P, Klarnet J, Suguwara H, Schultz K, Cheever M, Riddell S (1990) Requirements for antigen-specific induction and expression of CD4 and CD8 T-cell responses to tumors. In: Lotze M, Finn O (eds) Cellular immunity and the immunotherapy of cancer. Wiley-Liss, New York, pp 235–242

    Google Scholar 

  10. 10.

    Hammerling G, Klar D, Pulm W, Momberg F, Moldenhauer G (1987) The influence of major histocompatability complex class I antigens on tumor growth and metastasis. Biochim Biophys Acta 907: 245

    Google Scholar 

  11. 11.

    Hui K, Grosveld F, Festenstein H (1984) Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation. Nature 311: 750

    Google Scholar 

  12. 12.

    James R, Edwards S, Hui K, Bassett P, Grosveld F (1991) The effect of class II gene transfection on the tumourigenicity of the H-2K negative mouse leukaemia cell line K36.16. Immunology 72: 213

    Google Scholar 

  13. 13.

    Kaplan P, Anderson M, Ozanne B (1982) Transforming growth factor(s) production enables cells to grow in the absence of serum: an autocrine system. Proc Natl Acad Sci USA 79: 485

    Google Scholar 

  14. 14.

    Ling PD, Warren M, Vogel S (1985) Antagonistic effect of interferon-beta on the interferon-gamma induced expression of Ia antigens in murine macrophages. J Immunol 135: 1857

    Google Scholar 

  15. 15.

    Massague J (1984) Type β transforming growth factor from feline sarcoma virus-transformed rat cells: isolation and biological properties. J Biol Chem 259: 9756

    Google Scholar 

  16. 16.

    Morris A, Tomkins P (1989) Interactions of interferon in the induction of histocompatability antigens in mouse fibroblasts and glial cells. Immunology 67: 537

    Google Scholar 

  17. 17.

    Morris A, Ward G, Bateman W (1989) Interaction of v-Ki-ras oncogene and interferon gamma in the control of histocompatability antigen expression in mouse fibroblasts. Cell Immunol 120: 470

    Google Scholar 

  18. 18.

    Ostrand-Rosenberg S, Thakur A, Clements V (1990) Rejection of mouse sarcoma cells after transfection of MHC class II genes. J Immunol 144: 4068

    Google Scholar 

  19. 19.

    Owen R, Ostrowski M (1990) Transcriptional activation of a conserved sequence element byras requires a nuclear factor distinct from c-fos or c-jun. Proc Natl Acad Sci USA 87: 3866

    Google Scholar 

  20. 20.

    Ozanne B, Fulton R, Kaplan P (1980) Kirsten murine sarcoma virus transformed cell lines and a spontaneously transformed rat cell line produce transforming factors. J Cell Physiol 105: 163

    Google Scholar 

  21. 21.

    Reznikoff CH, Brankow D, Heidelberger C (1973) Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to post confluence inhibition of division. Cancer Res 33: 3231

    Google Scholar 

  22. 22.

    Rosenthal A, Lindquist P, Bringman T, Goeddel D, Derynck R (1986) Expression in rat fibroblasts of a human transforming growth factor-α cDNA results in transformation. Cell 46: 301

    Google Scholar 

  23. 23.

    Spitalny G, Havell E (1984) Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activity. J Exp Med 159: 1560

    Google Scholar 

  24. 24.

    Tanaka K, Hayashi H, Hamada C, Khoury G, Jay G (1986) Expression of major histocompatability complex class I antigens as a strategy for the potentiation of immune recognition of tumor cells. Proc Natl Acad Sci USA 83: 8723

    Google Scholar 

  25. 25.

    Todd I, Hammond L, James R, Feldmann M, Bottazzo G (1990) Epidermal growth factor and transforming growth factor-alpha suppress HLA class II induction in human thyroid epithelial cells. Immunology 69: 91

    Google Scholar 

  26. 26.

    Tomkins PT, Ward G, Morris A (1988) Role of interferon gamma in T-cell responses to Semliki Forest virus infected murine brain cells. Immunology 63: 355

    Google Scholar 

  27. 27.

    Wahl S, McCartney-Francis N, Mergenhagen S (1989) Inflammatory and immunoregulatory roles of TGF-β. Immunol Today 10: 258

    Google Scholar 

  28. 28.

    Wallich R, Bulbuc N, Hammerling G, Katzav S, Segal S, Feldman M (1985) Abrogation of metastatic properties of tumour cells by de novo expression of H-2K antigens following H-2 gene transfection. Nature 315: 301

    Google Scholar 

  29. 29.

    Yeoman H, Robins A (1988) The effect of interferon gamma treatment of rat tumour cells on their susceptibility to natural killer cell, macrophage and T-cell killing. Immunology 63: 291

    Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Wendy J. Bateman.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Morris, A.G., Darley, R.L. & Bateman, W.J. The loss of class II MHC antigen expression byras-transformed murine fibroblasts passaged as tumours correlates with increased tumorigenicity but is not mediated by T cells. Cancer Immunol Immunother 35, 46–52 (1992).

Download citation

Key words

  • ras
  • MHC
  • interferon γ
  • Tumorigenicity
  • T cells