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SV40 T-antigen is a histocompatibility antigen of SV40-transgenic mice

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Abstract

Although the extensive family of non-H-2 histocompatibility (H) antigens provides a formidable barrier to transplantation, the origin of their encoding genes are unknown. Recent studies have demonstrated both the linkage between H genes and retroviral sequences and the ability of integrated Moloney-murine leukemia virus to encode what is operationally defined as a non-H-2 H antigen. The experiments described in this communication reveal that skin grafts from an SV40 T-antigen transgenic C57BL/6 mouse strain are rejected by coisogenic C57BL/6 recipients with a median survival time of 49 days, which is comparable to those of many previously defined non-H-2 H antigens. The specificity of this response for SV40 T-antigen was demonstrated by the identification of SV40 T-antigen-specific cytolytic T lymphocytes and antibodies in multiply-grafted recipients. Although these cytolytic T lymphocytes could detect SV40 T-antigen on syngeneic SV40-transformed fibroblasts, they neither could be stimulated by splenic lymphocytes from T-antigen transgenics nor could they lyse lymphoblast targets from T-antigen transgenics. These observations suggest a limited tissue distribution of SV40 T-antigen in these transgenics. These results confirm the role of viral genes in the determination of non-H-2 histocompatibility antigenes by the strict criteria that such antigenes stimulate (1) tissue graft rejection and (2) generation of cytolytic T lymphocytes. Furthermore, they suggest that the SV40 enhancer and promoter region can target expression of SV-40 T-antigen to skin cells of transgenic animals.

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References

  • Bailey, D.: Heritable histocompatibility changes: lysogeny in mice? Transplantation 4: 482–488, 1966

    Google Scholar 

  • Bailey, D.: Genetics of histocompatibility in mice. I. New loci and congenic lines. Immunogenetics 2: 249–256, 1975

    Google Scholar 

  • Bailey, D. and Usama, B.: A rapid method of grafting skin on tails of mice. Transplant. Bull. 7: 424–428, 1960

    Google Scholar 

  • Brinster, R., Howe, C., Messing, A., Van Dyke, T., Levine, A., and Palmiter, R.: Transgenic mice harboring SV40 T-antigen genes develop characteristic brain tumors. Cell 37: 376–387, 1984

    Google Scholar 

  • Colombo, M., Jaenisch, R., and Wettstein, P.: Endogenous retroviruses lead to the expression of a histocompatibility antigen detectable by skin graft rejection. Proc. Natl. Acad. Sci. U.S.A. 84: 189–193, 1987a

    Google Scholar 

  • Colombo, M. P., Melvold, R. W., and Wettstein, P. J.: Inheritance of a mutant histocompatibility gene and a new mammary tumor virus genome in the B6.KH-84 mouse strain. Immunogenetics 26: 99–104, 1987b

    Google Scholar 

  • Faas, S. J., Pan, S., Pinkert, C. A., Brinster, R. L., and Knowles, B. B.: SV40-transgenic mice that develop tumors are specifically tolerant to SV40 T-antigen. J. Exp. Med. 165: 417–427, 1987

    Google Scholar 

  • Gooding, L. J.: Specificities of killing by cytotoxic lymphocytes generated in vivo and in vitro to syngeneic SV40 transformed cells. J. Immunol. 118: 920–925, 1977

    Google Scholar 

  • Graff, R. and Bailey, D.: The non-H-2 histocompatibility loci and their antigens. Transplant. Rev. 15: 26–49, 1973

    Google Scholar 

  • Jaenisch, R., Jahner, D., Nobis, P., Simon, I, Lohler, J., Harbers, K., and Grotkopp, D.: Chromosomal position and activation of retroviral genomes inserted into the germ line of mice. Cell 24: 519–529, 1981

    Google Scholar 

  • Knowles, B. B., Koncar, M., Pfizenmaier, K., Solter, D., Aden, D., and Trinchieri, G.: Genetic control of cytotoxic T cell response to SV40 tumor-associated specific antigen. J. Immunol. 122: 1798–1806, 1979

    Google Scholar 

  • Meruelo, D., Rossomando, A., Offer, M., Buxbaum, J., and Pellicer, A.: Association of endogenous viral loci with genes encoding murine histocompatibility and lymphocyte differentiation antigens. Proc. Mad. Acad. Sci. U.S.A. 80: 5032–5036, 1983

    Google Scholar 

  • Palmiter, R. D., Howe, C. Y., Messing, A., and Brinster, R. L.: SV40 enhancer and large-T antigen are instrumental in development of choroid plexus tumors in transgenic mice. Nature 316: 457–460, 1985

    Google Scholar 

  • Pan, S. and Knowles, B. B.: Monoclonal antibody to SV40 T-antigen blocks lysis of cloned cytotoxic T-cell line specific for SV40 TASA. Virology 125: 1–6, 1983

    Google Scholar 

  • Rammensee, H., Robinson, P., Crisanti, A., and Bevan, M.: Restricted recognition of beta 2-microglobulin by cytotoxic T lymphocytes. Nature 319: 502–504, 1987

    Google Scholar 

  • Rossomando, A. and Meruelo, D.: Viral sequences are associated with many histocompatibility genes. Immunogenetics 23: 233–245, 1986

    Google Scholar 

  • Scheid, M., Boyse, E., Carswell, E., and Old, L.: Serologically demonstrable alloantigens of mouse epidermal cells. J. Exp. Med. 135: 938–955, 1972

    Google Scholar 

  • Townsend, A. R. M., Gotch, F. M., and Davey, J.: Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell 42: 457–467, 1985

    Google Scholar 

  • Wettstein, P. J. and Colombo, M. P.: Immunodominance in the T cell response to multiple non-H-2 histocompatibility antigens. IV. Partial tissue distribution and mapping of immunodominant antigens. J. Immunol. 139: 2166–2171, 1987

    Google Scholar 

  • Wettstein, P. J. and Melvold, R. W.: Xenotropic virus-related restriction patterns of non-H-2 histocompatibility mutant mice strains. Immunogenetics 23: 156–163, 1986

    Google Scholar 

  • Wettstein, P. J., Haughton, G., and Frelinger, J.: H-2 effects on cell-cell interactions in the response to single non-H-2 alloantigens. Donor H-2D region control of H-7.1-immunogenicity and lack of restriction in vivo. J. Exp. Med. 146: 1346–1355, 1977

    Google Scholar 

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Wettstein, P.J., Jewett, L., Faas, S. et al. SV40 T-antigen is a histocompatibility antigen of SV40-transgenic mice. Immunogenetics 27, 436–441 (1988). https://doi.org/10.1007/BF00364430

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  • DOI: https://doi.org/10.1007/BF00364430

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