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. 1985 Jul 1;162(1):128–144. doi: 10.1084/jem.162.1.128

Characterization of gP85gag as an antigen recognized by Moloney leukemia virus-specific cytolytic T cell clones that function in vivo

PMCID: PMC2187707  PMID: 3891902

Abstract

The gag membrane protein gP85gag, encoded by Moloney murine leukemia virus (M-MLV), was identified as a target molecule recognized by Moloney murine sarcoma virus--M-MLV (M-MSV--M-MLV)-specific cytolytic T lymphocyte (CTL) clones. Target cells infected with Ab-X-MLV, an M-MLV- derived mutant virus not encoding gP85gag, were not lysed by the CTL clones. The same CTL clones were shown previously to induce the destruction of M-MLV-induced tumor cells in the peritoneal cavity. We have now characterized CTL-resistant antigen-loss tumor cell variants that have lost the surface antigen, but which retain transcriptionally silent M-MLV genomes. A cloned antigen-loss variant that reverted in vitro to the CTL-susceptible phenotype reexpressed M-MLV genomes that had undergone an insertion event in the region of the viral DNA coding for the gag membrane protein. Intravenous injection of virus-specific CTL clones inhibited tumor formation in mice injected subcutaneously with M-MSV--M-MLV.

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Selected References

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  1. Alaba O., Rogers M. J., Law L. W. Rauscher leukemia virus-induced tumor antigens: complete separation from gp70, p30 and H-2. Int J Cancer. 1979 Nov 15;24(5):608–615. doi: 10.1002/ijc.2910240514. [DOI] [PubMed] [Google Scholar]
  2. Byrne J. A., Oldstone M. B. Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo. J Virol. 1984 Sep;51(3):682–686. doi: 10.1128/jvi.51.3.682-686.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chatis P. A., Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408–4411. doi: 10.1073/pnas.80.14.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chesebro B., Portis J. L., Wehrly K., Nishio J. Effect of murine host genotype on MCF virus expression, latency, and leukemia cell type of leukemias induced by Friend murine leukemia helper virus. Virology. 1983 Jul 15;128(1):221–233. doi: 10.1016/0042-6822(83)90332-x. [DOI] [PubMed] [Google Scholar]
  5. Collavo D., Colombatti A., Biasi G., Chieco-Bianchi L., Davies A. J. Immune reactivity in the Moloney strain of murine sarcoma virus oncogenesis: requirement of thymus-derived lymphocytes for in vivo protection. J Natl Cancer Inst. 1976 Mar;56(3):603–608. doi: 10.1093/jnci/56.3.603. [DOI] [PubMed] [Google Scholar]
  6. Collins J. K., Britt W. J., Chesebro B. Cytotoxic T lymphocyte recognition of gp70 on Friend virus-induced erythroleukemia cell clones. J Immunol. 1980 Sep;125(3):1318–1324. [PubMed] [Google Scholar]
  7. Copeland N. G., Bedigian H. G., Thomas C. Y., Jenkins N. A. DNAs of two molecularly cloned endogenous ecotropic proviruses are poorly infectious in DNA transfection assays. J Virol. 1984 Feb;49(2):437–444. doi: 10.1128/jvi.49.2.437-444.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Corcoran L. M., Adams J. M., Dunn A. R., Cory S. Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion. Cell. 1984 May;37(1):113–122. doi: 10.1016/0092-8674(84)90306-4. [DOI] [PubMed] [Google Scholar]
  9. Cuypers H. T., Selten G., Quint W., Zijlstra M., Maandag E. R., Boelens W., van Wezenbeek P., Melief C., Berns A. Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region. Cell. 1984 May;37(1):141–150. doi: 10.1016/0092-8674(84)90309-x. [DOI] [PubMed] [Google Scholar]
  10. Dailey M. O., Pillemer E., Weissman I. L. Protection against syngeneic lymphoma by a long-lived cytotoxic T-cell clone. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5384–5387. doi: 10.1073/pnas.79.17.5384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Edwards S. A., Fan H. Sequence relationship of glycosylated and unglycosylated gag polyproteins of Moloney murine leukemia virus. J Virol. 1980 Jul;35(1):41–51. doi: 10.1128/jvi.35.1.41-51.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Engers H. D., Sorenson G. D., Terres G., Horvath C., Brunner K. T. Functional activity in vivo of effector T cell populations. I. Antitumor activity exhibited by allogeneic mixed leukocyte culture cells. J Immunol. 1982 Sep;129(3):1292–1298. [PubMed] [Google Scholar]
  13. Enjuanes L., Lee J. C., Ihle J. N. Antigenic specificities of the cellular immune response of C57BL/6 mice to the Moloney leukemia/sarcoma virus complex. J Immunol. 1979 Feb;122(2):665–674. [PubMed] [Google Scholar]
  14. Ertl H. C., Finberg R. W. Characteristics and functions of Sendai virus-specific T-cell clones. J Virol. 1984 May;50(2):425–431. doi: 10.1128/jvi.50.2.425-431.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Evans L. H., Cloyd M. W. Generation of mink cell focus-forming viruses by Friend murine leukemia virus: recombination with specific endogenous proviral sequences. J Virol. 1984 Mar;49(3):772–781. doi: 10.1128/jvi.49.3.772-781.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fan H., Chute H., Chao E., Feuerman M. Construction and characterization of Moloney murine leukemia virus mutants unable to synthesize glycosylated gag polyprotein. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5965–5969. doi: 10.1073/pnas.80.19.5965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Flyer D. C., Burakoff S. J., Faller D. V. Cytotoxic T lymphocyte recognition of transfected cells expressing a cloned retroviral gene. 1983 Oct 27-Nov 2Nature. 305(5937):815–818. doi: 10.1038/305815a0. [DOI] [PubMed] [Google Scholar]
  18. Gomard E., Levy J. P., Plata F., Henin Y., Duprez V., Bismuth A., Reme T. Studies on the nature of the cell surface antigen reacting with cytolytic T lymphocytes in murine oncornavirus-induced tumors. Eur J Immunol. 1978 Apr;8(4):228–236. doi: 10.1002/eji.1830080403. [DOI] [PubMed] [Google Scholar]
  19. Gorczynski R. M., Knight R. A. Cell-mediated immunity to Moloney sarcoma virus in mice. II. Analysis of antigenic specificities involved in T lymphocyte-mediated in vivo rejection of murine sarcoma virus-induced tumors. Eur J Immunol. 1975 Feb;5(2):148–155. doi: 10.1002/eji.1830050214. [DOI] [PubMed] [Google Scholar]
  20. Green W. R. H-2-restricted cytolytic T lymphocytes specific for a subclass of AKR endogenous leukemia virus-induced tumors: correlation of tumor cell susceptibility with expression of the gross cell surface antigen. J Immunol. 1980 Dec;125(6):2584–2590. [PubMed] [Google Scholar]
  21. Hartley J. W., Wolford N. K., Old L. J., Rowe W. P. A new class of murine leukemia virus associated with development of spontaneous lymphomas. Proc Natl Acad Sci U S A. 1977 Feb;74(2):789–792. doi: 10.1073/pnas.74.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Herr W. Nucleotide sequence of AKV murine leukemia virus. J Virol. 1984 Feb;49(2):471–478. doi: 10.1128/jvi.49.2.471-478.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jaenisch R., Jähner D. Methylation, expression and chromosomal position of genes in mammals. Biochim Biophys Acta. 1984 May 15;782(1):1–9. doi: 10.1016/0167-4781(84)90099-x. [DOI] [PubMed] [Google Scholar]
  24. Leclerc J. C., Cantor H. T cell-mediated immunity to oncornavirus-induced tumors. II. Ability of different T cell sets to prevent tumor growth in vivo. J Immunol. 1980 Feb;124(2):851–854. [PubMed] [Google Scholar]
  25. Ledbetter J. A., Nowinski R. C., Eisenman R. N. Biosynthesis and metabolism of viral proteins expressed on the surface of murine leukemia virus-infected cells. Virology. 1978 Nov;91(1):116–129. doi: 10.1016/0042-6822(78)90360-4. [DOI] [PubMed] [Google Scholar]
  26. Lee J. C., Ihle J. N. Chronic immune stimulation is required for Moloney leukaemia virus-induced lymphomas. Nature. 1981 Jan 29;289(5796):407–409. doi: 10.1038/289407a0. [DOI] [PubMed] [Google Scholar]
  27. Lenz J., Celander D., Crowther R. L., Patarca R., Perkins D. W., Haseltine W. A. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. 1984 Mar 29-Apr 4Nature. 308(5958):467–470. doi: 10.1038/308467a0. [DOI] [PubMed] [Google Scholar]
  28. Lieberman M. M., Ayala E. Active and passive immunity against Pseudomonas aeruginosa with a ribosomal vaccine and antiserum in C3H/HeJ mice. J Immunol. 1983 Jul;131(1):1–3. [PubMed] [Google Scholar]
  29. Lin Y. L., Askonas B. A. Biological properties of an influenza A virus-specific killer T cell clone. Inhibition of virus replication in vivo and induction of delayed-type hypersensitivity reactions. J Exp Med. 1981 Aug 1;154(2):225–234. doi: 10.1084/jem.154.2.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Maryanski J. L., Marchand M., Uyttenhove C., Boon T. Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. VI. Occasional escape from host rejection due to antigen-loss secondary variants. Int J Cancer. 1983 Jan 15;31(1):119–123. doi: 10.1002/ijc.2910310119. [DOI] [PubMed] [Google Scholar]
  31. Mathey-Prevot B., Shibuya M., Samarut J., Hanafusa H. Revertants and partial transformants of rat fibroblasts infected with Fujinami sarcoma virus. J Virol. 1984 May;50(2):325–334. doi: 10.1128/jvi.50.2.325-334.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nexø B. A., Ulrich K. Variants of type-C retroviruses from DBA/2 mice: protein-structural and biological properties. Virology. 1983 Mar;125(2):454–467. doi: 10.1016/0042-6822(83)90216-7. [DOI] [PubMed] [Google Scholar]
  33. O'Donnell P. V., Stockert E., Obata Y., DeLeo A. B., Old L. J. Murine-leukemia-virus-related cell-surface antigens as serological markers of AKR ecotropic, xenotropic, and dualtropic viruses. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):1255–1264. doi: 10.1101/sqb.1980.044.01.136. [DOI] [PubMed] [Google Scholar]
  34. Old L. J., Boyse E. A., Stockert E. The G (Gross) leukemia antigen. Cancer Res. 1965 Jul;25(6):813–819. [PubMed] [Google Scholar]
  35. Plata F., Cerottini J. C., Brunner K. T. Primary and secondary in vitro generation of cytolytic T lymphocytes in the murine sarcoma virus system. Eur J Immunol. 1975 Apr;5(4):227–233. doi: 10.1002/eji.1830050402. [DOI] [PubMed] [Google Scholar]
  36. Quint W., Boelens W., van Wezenbeek P., Cuypers T., Maandag E. R., Selten G., Berns A. Generation of AKR mink cell focus-forming viruses: a conserved single-copy xenotrope-like provirus provides recombinant long terminal repeat sequences. J Virol. 1984 May;50(2):432–438. doi: 10.1128/jvi.50.2.432-438.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Quint W., Quax W., van der Putten H., Berns A. Characterization of AKR murine leukemia virus sequences in AKR mouse substrains and structure of integrated recombinant genomes in tumor tissues. J Virol. 1981 Jul;39(1):1–10. doi: 10.1128/jvi.39.1.1-10.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Reddy E. P., Smith M. J., Srinivasan A. Nucleotide sequence of Abelson murine leukemia virus genome: structural similarity of its transforming gene product to other onc gene products with tyrosine-specific kinase activity. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3623–3627. doi: 10.1073/pnas.80.12.3623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Roblin R., Young J. M., Mural R. J., Bell T. E., Ihle J. N. Molecular cloning and characterization of murine leukemia virus-related DNA sequences from C3H/HeN mouse DNA. J Virol. 1982 Jul;43(1):113–126. doi: 10.1128/jvi.43.1.113-126.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Saris C. J., van Eenbergen J., Liskamp R. M., Bloemers H. P. Structure of glycosylated and unglycosylated gag and gag-pol precursor proteins of Moloney murine leukemia virus. J Virol. 1983 Jun;46(3):841–859. doi: 10.1128/jvi.46.3.841-859.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sethi K. K., Omata Y., Schneweis K. E. Protection of mice from fatal herpes simplex virus type 1 infection by adoptive transfer of cloned virus-specific and H-2-restricted cytotoxic T lymphocytes. J Gen Virol. 1983 Feb;64(Pt 2):443–447. doi: 10.1099/0022-1317-64-2-443. [DOI] [PubMed] [Google Scholar]
  42. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
  43. Stukart M. J., Boes J., Melief C. J. Immunity against Moloney sarcoma virus in H-2Db mutant bm14 mice. Unimpaired tumor immunity despite absence of a virus-specific cytotoxic T-cell response. Int J Cancer. 1984 Feb 15;33(2):265–269. doi: 10.1002/ijc.2910330216. [DOI] [PubMed] [Google Scholar]
  44. Stukart M. J., Vos A., Melitef C. J. Cytotoxic T cell response against lymphoblasts infected with Moloney (Abelson) murine leukemia virus. Methodological aspects and H-2 requirements. Eur J Immunol. 1981 Mar;11(3):251–257. doi: 10.1002/eji.1830110316. [DOI] [PubMed] [Google Scholar]
  45. Taniyama T., Holden H. T. In vitro induction of T-lymphocyte-mediated cytotoxicity by infectious murine type C oncornaviruses. J Exp Med. 1979 Dec 1;150(6):1367–1382. doi: 10.1084/jem.150.6.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Thomas C. Y., Khiroya R., Schwartz R. S., Coffin J. M. Role of recombinant ecotropic and polytropic viruses in the development of spontaneous thymic lymphomas in HRS/J mice. J Virol. 1984 May;50(2):397–407. doi: 10.1128/jvi.50.2.397-407.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Urban J. L., Schreiber H. Selection of macrophage-resistant progressor tumor variants by the normal host. Requirement for concomitant T cell-mediated immunity. J Exp Med. 1983 Feb 1;157(2):642–656. doi: 10.1084/jem.157.2.642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Van Beveren C., van Straaten F., Galleshaw J. A., Verma I. M. Nucleotide sequence of the genome of a murine sarcoma virus. Cell. 1981 Nov;27(1 Pt 2):97–108. doi: 10.1016/0092-8674(81)90364-0. [DOI] [PubMed] [Google Scholar]
  49. Van Zaane D., Dekker-Michielsen J. A., Bloemers H. P. Virus-specific precursor polypeptides in cells infected with Rauscher leukemia virus: synthesis, identification, and processing. Virology. 1976 Nov;75(1):113–129. doi: 10.1016/0042-6822(76)90011-8. [DOI] [PubMed] [Google Scholar]
  50. Weiss A., Brunner K. T., MacDonald H. R., Cerottini J. C. Antigenic specificity of the cytolytic T lymphocyte response to murine sarcoma virus-induced tumors. III. Characterization of cytolytic T lymphocyte clones specific for Moloney leukemia virus-associated cell surface antigens. J Exp Med. 1980 Nov 1;152(5):1210–1225. doi: 10.1084/jem.152.5.1210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Weissman I. L., McGrath M. S. Retrovirus lymphomagenesis: relationship of normal immune receptors to malignant cell proliferation. Curr Top Microbiol Immunol. 1982;98:103–112. doi: 10.1007/978-3-642-68369-5_8. [DOI] [PubMed] [Google Scholar]
  52. Zubler R. H. Polyclonal B cell responses in the presence of defined filler cells: complementary effects of lipopolysaccharide and anti-immunoglobulin antibodies. Eur J Immunol. 1984 Apr;14(4):357–363. doi: 10.1002/eji.1830140415. [DOI] [PubMed] [Google Scholar]
  53. van der Hoorn F. A., Saris C. J., Bloemers H. P. 3Y1 rat cells are defective in processing of the envelope precursor protein of AKR virus. Virology. 1983 Jan 30;124(2):462–466. doi: 10.1016/0042-6822(83)90361-6. [DOI] [PubMed] [Google Scholar]
  54. van der Putten H., Quint W., van Raaij J., Maandag E. R., Verma I. M., Berns A. M-MuLV-induced leukemogenesis: integration and structure of recombinant proviruses in tumors. Cell. 1981 Jun;24(3):729–739. doi: 10.1016/0092-8674(81)90099-4. [DOI] [PubMed] [Google Scholar]

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