Abstract
AKR leukemia cell lines differing in the amount of H-2K and H-2D antigens expressed on the cell surface were used to assess cell-mediated immune responses in syngeneic mice against Gross/AKR murine leukemia virus (MuLV)-induced tumors. Leukemic cells with reduced expression of H-2Kk antigens were inactive as inducers of Gross-MuLV/H-2k-specific cytotoxic T lymphocytes (CTL) and resistant to lysis by CTL raised against H-2Kk positive AKR leukemia cells. H-2Kk positive leukemias induced cytotoxic effectors, which upon restimulation in vitro, lysed the stimulating and other H-2Kk positive leukemia cells. In antibody inhibition experiments, T-cell-mediated cytotoxicity to these leukemias could only be inhibited by antisera and monoclonal antibodies specific for the H-2Kk antigens. Due to this specific role of H-2Kk antigens in T-cell cytotoxicity to Gross/AKR MuLV-induced tumors, reduced expression of H-2Kk antigens on spontaneous AKR leukemic cells could have important implications for surveillance of these neoplastic cells.
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Abbreviations
- CTL:
-
cytotoxic T lymphocytes
- MuLV:
-
murine leukemia virus
References
Bartlett, P. F. and Edidin, M.: Effect of the H-2 gene complex rates of fibroblast intercellular adhesion. J. Cell. Biol. 77: 377–388, 1978
Blank, K. J. and Lilly, F.: Evidence for an H-2/viral protein complex on the cell surface as the basis for the H-2 restriction of cytotoxicity. Nature 269: 808–809, 1977
Dalidius, T., Ahrlund-Richter, L., Merino, F., Klein, E., and Klein, G.: Reduced Immoral and cellular cytotoxic sensitivity in major histocompatibility variants of the YAC (Moloney) lymphoma. Immunogenetics 12: 371–380, 1981
DeBaetselier, P., Katzov, S., Govelik, E., Feldman, M., and Segal, S.: Differential expression of H-2 gene products in tumor cells is associated with their metastatic properties. Nature 288: 179–181, 1980
Degos, L., Pla, M., and Colombani, J. M.: H-2 restriction for lymphocyte homing into lymph nodes. Eur. J. Immunol. 9: 808–814, 1979
Doherty, P. C., Blanden, R. V., and Zinkernagel, R. M.: Specificity of virus immune effector T cells for H-2K or H-2D compatible interactions. Implications for H-antigen diversity. Transplant. Rev. 29: 89–124, 1976
Festenstein, H. and Schmidt, W.: Variation in MHC antigenic profiles of tumor cells and its biological consequences. Immunol. Rev. 60: 85–127, 1981
Gmür, R., Scher, D., and Knowles, B. B.: Independent regulation of H-2K and H-2D gene expression in murine teratocarcinome somatic cell hybrids. J. Exp. Med. 151: 1349–1359, 1980
Gomard, E., Duprez, V., Henin, Y., and Levy, J. P.: H-2 region products as determinant in immune cytolysis of syngeneic tumor cells by anti MSV T lymphocytes. Nature 260: 707–709, 1976
Greaves, M.: Analysis of the clinical and biological significance of lymphoid phenotypes in acute leukaemia. Cancer Res. 41: 4752–4768, 1981
Greenberg, P. D., Cheever, M. A., and Fefer, A.: Distinct phenotypic expression of immunogenicity and immunosensitivity in sublines of a tumor. J. Immunol. 126: 200–205, 1981
Haran-Ghera, N.: Potential leukaemic cells among bone marrow cells of young AKR/J mice. Proc. Natl. Acad. Sci. U.S.A. 77: 2923–2926, 1980
Lemke, H., Hämmerling, G. J., Hohmann, L., and Rajewsky, K.: Hybrid cell lines secreting monoclonal antibody specific for major histocompatibility antigens of the mouse. Nature 271: 249–251, 1978
Lengerova, A., Zeleny, V., Haskovec, C., and Hilgert, I.: Search for the physiological function of H-2 gene products. Eur. J. Imunol. 7: 62–69, 1977
Lilly, F.: The inheritance of susceptibility to the Gross leukaemia virus in mice. Genetics 53: 529–539, 1968
McGrath, M. S. and Weissman, I. L.: AKR leukaemogenesis. Identification and biological significance of thymic lymphoma receptors for AKR retroviruses. Cell 17: 65–75, 1979
Ohno, S.: The original function of MHC antigens as the general plasma membrane anchorage site of organogenesis-directing proteins. Immunol. Rev. 33: 59–69, 1977
Ozato, K., Mayer, N., and Sachs, D. H.: Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and la antigens. J. Immunol. 124: 533–540, 1980
Plata, F.: Specificity studies of cytolytic T lymphocytes directed against marine leukaemia virus-induced tumors. Analysis by monoclonal cytolytic T lymphocytes. J. Exp. Med. 155: 1050–1062, 1982
Schmidt, W., Atfield, G., and Festenstein, H.: Loss of H-2k gene product(s) from an AKR spontaneous leukaemia. Immunogenetlcs 8: 311–321, 1979
Schmidt, W., Leben, L., Atfield, G., and Festenstein, H.: Variation of expression of histocompatibility antigens on tumor cells: Absence of H-2Kk gene products from a Gross-virus induced leukaemia in BALB.K. Iminunogenetics 14: 323–339, 1981a
Schmidt, W., Alonzo, A., Leben, L., and Festenstein, H.: Differential regulation of H-2 antigen expression in tumors and its biological consequences. Transplant. Proc. 13: 1814–1818, 1981b
Scollay, R. S., Jacobs, L., Jerabek, L., Butcher, E., and Weissman, I: T cell maturation: Thymocyte and thymus migrant subpopulations defined with monoclonal antibodies to MHC region antigens. J. Immunol. 124: 2845–2853, 1980
Testorelli, C., Marelli, O., Schmidt, W., and Festenstein, H.: Changes in H-2 antigen expression on a marine spontaneous leukaemia (K36) detected by a cell-mediated cytotoxicity assay. J. Immunogenet. 7: 19–29, 1980
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Schmidt, W., Festenstein, H. Resistance to cell-mediated cytotoxicity is correlated with reduction of H-2K gene products in AKR leukemia. Immunogenetics 16, 257–264 (1982). https://doi.org/10.1007/BF00343314
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DOI: https://doi.org/10.1007/BF00343314