Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1993 Aug;67(8):4533–4542. doi: 10.1128/jvi.67.8.4533-4542.1993

Multiplicity of virus-encoded helper T-cell epitopes expressed on FBL-3 tumor cells.

M Iwashiro 1, T Kondo 1, T Shimizu 1, H Yamagishi 1, K Takahashi 1, Y Matsubayashi 1, T Masuda 1, A Otaka 1, N Fujii 1, A Ishimoto 1, et al.
PMCID: PMC237837  PMID: 7687300

Abstract

To identify retroviral antigenic determinants recognized by CD4+ T helper cells during tumor rejection, we established four noncytolytic, helper-type, CD4+ T-cell clones by limiting dilution cultures of mixed lymphocyte-tumor cultures from mice immune to a Friend virus-induced tumor, FBL-3. Among these, three T helper cell clones were isolated from C57BL/6 mice and the fourth was isolated from a (BALB/c x C57BL/6)F1 mouse. All these clones proliferated in response to the immunizing FBL-3 tumor cells in a major histocompatibility complex class II-restricted manner. Each clone expressed a distinct T-cell receptor with a characteristic combination of alpha and beta chains. The localization of helper T-cell determinants on viral proteins was analyzed with recombinant vaccinia viruses expressing Friend murine leukemia virus (F-MuLV) gag or env genes or shorter fragments of the env gene. Epitopes recognized by these T-cell clones were mapped to at least two distinct portions in the env region of the F-MuLV genome. These epitopes were identified more precisely with synthetic peptides derived from the F-MuLV envelope protein sequence. One of these epitopes was common to Friend and Moloney MuLVs and was located in the N-terminal region of the gp70 glycoprotein at amino acids 122 to 141. The second epitope, which was recognized in the context of hybrid I-Eb/d major histocompatibility complex class II molecule, was located close to the C-terminal end of gp70 at amino acids 462 to 479. In addition, a possible third epitope was located in the N-terminal half of the gp70 sequence and differed from the first epitope in that it was not cross-reactive with the Moloney MuLV envelope protein.

Full text

PDF
4533

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adachi A., Sakai K., Kitamura N., Nakanishi S., Niwa O., Matsuyama M., Ishimoto A. Characterization of the env gene and long terminal repeat of molecularly cloned Friend mink cell focus-inducing virus DNA. J Virol. 1984 Jun;50(3):813–821. doi: 10.1128/jvi.50.3.813-821.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blank K. J., 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. 1977 Oct 27;269(5631):808–809. doi: 10.1038/269808a0. [DOI] [PubMed] [Google Scholar]
  3. Bookman M. A., Swerdlow R., Matis L. A. Adoptive chemoimmunotherapy of murine leukemia with helper T lymphocyte clones. J Immunol. 1987 Nov 1;139(9):3166–3170. [PubMed] [Google Scholar]
  4. Chakrabarti S., Brechling K., Moss B. Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. Mol Cell Biol. 1985 Dec;5(12):3403–3409. doi: 10.1128/mcb.5.12.3403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chesebro B., Britt W., Evans L., Wehrly K., Nishio J., Cloyd M. Characterization of monoclonal antibodies reactive with murine leukemia viruses: use in analysis of strains of friend MCF and Friend ecotropic murine leukemia virus. Virology. 1983 May;127(1):134–148. doi: 10.1016/0042-6822(83)90378-1. [DOI] [PubMed] [Google Scholar]
  6. Chesebro B., Wehrly K., Cloyd M., Britt W., Portis J., Collins J., Nishio J. Characterization of mouse monoclonal antibodies specific for Friend murine leukemia virus-induced erythroleukemia cells: friend-specific and FMR-specific antigens. Virology. 1981 Jul 15;112(1):131–144. doi: 10.1016/0042-6822(81)90619-x. [DOI] [PubMed] [Google Scholar]
  7. Chien Y., Becker D. M., Lindsten T., Okamura M., Cohen D. I., Davis M. M. A third type of murine T-cell receptor gene. Nature. 1984 Nov 1;312(5989):31–35. doi: 10.1038/312031a0. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Earl P. L., Moss B., Morrison R. P., Wehrly K., Nishio J., Chesebro B. T-lymphocyte priming and protection against Friend leukemia by vaccinia-retrovirus env gene recombinant. Science. 1986 Nov 7;234(4777):728–731. doi: 10.1126/science.3490689. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Fujiwara H., Fukuzawa M., Yoshioka T., Nakajima H., Hamaoka T. The role of tumor-specific Lyt-1+2- T cells in eradicating tumor cells in vivo. I. Lyt-1+2- T cells do not necessarily require recruitment of host's cytotoxic T cell precursors for implementation of in vivo immunity. J Immunol. 1984 Sep;133(3):1671–1676. [PubMed] [Google Scholar]
  12. Glynn J. P., McCoy J. L., Fefer A. Cross-resistance to the transplantation of syngeneic Friend, Moloney, and Rauscher virus-induced tumors. Cancer Res. 1968 Mar;28(3):434–439. [PubMed] [Google Scholar]
  13. Gomard E., Hénin Y., Colombani M. J., Lévy J. P. Immune response genes control T killer cell response against Moloney tumor antigen cytolysis regulating reactions against the best available H-2 + viral antigen association. J Exp Med. 1980 Jun 1;151(6):1468–1476. doi: 10.1084/jem.151.6.1468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Greenberg P. D., Cheever M. A., Fefer A. Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2- lymphocytes. J Exp Med. 1981 Sep 1;154(3):952–963. doi: 10.1084/jem.154.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hedrick S. M., Nielsen E. A., Kavaler J., Cohen D. I., Davis M. M. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature. 1984 Mar 8;308(5955):153–158. doi: 10.1038/308153a0. [DOI] [PubMed] [Google Scholar]
  16. Hirama T., Takeshita S., Matsubayashi Y., Iwashiro M., Masuda T., Kuribayashi K., Yoshida Y., Yamagishi H. Conserved V(D)J junctional sequence of cross-reactive cytotoxic T cell receptor idiotype and the effect of a single amino acid substitution. Eur J Immunol. 1991 Feb;21(2):483–488. doi: 10.1002/eji.1830210234. [DOI] [PubMed] [Google Scholar]
  17. Ishimoto A., Maeda M. Studies on the susceptibility of C57BL/6 mice to Rauscher virus. I. Properties of Rauscher virus-induced C57BL/6 lymphomas. J Natl Cancer Inst. 1970 Feb;44(2):361–368. [PubMed] [Google Scholar]
  18. Klarnet J. P., Kern D. E., Okuno K., Holt C., Lilly F., Greenberg P. D. FBL-reactive CD8+ cytotoxic and CD4+ helper T lymphocytes recognize distinct Friend murine leukemia virus-encoded antigens. J Exp Med. 1989 Feb 1;169(2):457–467. doi: 10.1084/jem.169.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koch W., Hunsmann G., Friedrich R. Nucleotide sequence of the envelope gene of Friend murine leukemia virus. J Virol. 1983 Jan;45(1):1–9. doi: 10.1128/jvi.45.1.1-9.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Koop B. F., Wilson R. K., Wang K., Vernooij B., Zallwer D., Kuo C. L., Seto D., Toda M., Hood L. Organization, structure, and function of 95 kb of DNA spanning the murine T-cell receptor C alpha/C delta region. Genomics. 1992 Aug;13(4):1209–1230. doi: 10.1016/0888-7543(92)90039-u. [DOI] [PubMed] [Google Scholar]
  21. Kronenberg M., Siu G., Hood L. E., Shastri N. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annu Rev Immunol. 1986;4:529–591. doi: 10.1146/annurev.iy.04.040186.002525. [DOI] [PubMed] [Google Scholar]
  22. Levy J. P., Leclerc J. C. The murine sarcoma virus-induced tumor: exception or general model in tumor immunology? Adv Cancer Res. 1977;24:1–66. doi: 10.1016/s0065-230x(08)61012-x. [DOI] [PubMed] [Google Scholar]
  23. Manjunath R., Graziano R. F., Green W. R. The specificity of H-2-restricted cytotoxic T lymphocytes directed to AKR/Gross leukemia virus-induced tumors. III. Coordinate alterations in viral gp70 antigen expression and restoration of CTL-susceptibility to insusceptible variant tumors. J Immunol. 1986 Mar 15;136(6):2271–2279. [PubMed] [Google Scholar]
  24. Margalit H., Spouge J. L., Cornette J. L., Cease K. B., Delisi C., Berzofsky J. A. Prediction of immunodominant helper T cell antigenic sites from the primary sequence. J Immunol. 1987 Apr 1;138(7):2213–2229. [PubMed] [Google Scholar]
  25. Matis L. A., Ruscetti S. K., Longo D. L., Jacobson S., Brown E. J., Zinn S., Kruisbeek A. M. Distinct proliferative T cell clonotypes are generated in response to a murine retrovirus-induced syngeneic T cell leukemia: viral gp70 antigen-specific MT4+ clones and Lyt-2+ cytolytic clones which recognize a tumor-specific cell surface antigen. J Immunol. 1985 Jul;135(1):703–713. [PubMed] [Google Scholar]
  26. Matis L. A., Shu S., Groves E. S., Zinn S., Chou T., Kruisbeek A. M., Rosenstein M., Rosenberg S. A. Adoptive immunotherapy of a syngeneic murine leukemia with a tumor-specific cytotoxic T cell clone and recombinant human interleukin 2: correlation with clonal IL 2 receptor expression. J Immunol. 1986 May 1;136(9):3496–3501. [PubMed] [Google Scholar]
  27. Matsubayashi Y., Hirama T., Morioka A., Iwashiro M., Masuda T., Uchino H., Takeshita S., Yamagishi H., Udono H., Mieno M. Participation of a dominant cytotoxic T cell population defined by a monoclonal antibody in syngeneic anti-tumor responses. Eur J Immunol. 1990 Sep;20(9):2095–2103. doi: 10.1002/eji.1830200931. [DOI] [PubMed] [Google Scholar]
  28. Miyazawa M., Nishio J., Chesebro B. Genetic control of T cell responsiveness to the Friend murine leukemia virus envelope antigen. Identification of class II loci of the H-2 as immune response genes. J Exp Med. 1988 Nov 1;168(5):1587–1605. doi: 10.1084/jem.168.5.1587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Miyazawa M., Nishio J., Chesebro B. Protection against Friend retrovirus-induced leukemia by recombinant vaccinia viruses expressing the gag gene. J Virol. 1992 Jul;66(7):4497–4507. doi: 10.1128/jvi.66.7.4497-4507.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Miyazawa M., Nishio J., Wehrly K., Chesebro B. Influence of MHC genes on spontaneous recovery from Friend retrovirus-induced leukemia. J Immunol. 1992 Jan 15;148(2):644–647. [PubMed] [Google Scholar]
  31. OLD L. J., BOYSE E. A., STOCKERT E. TYPING OF MOUSE LEUKAEMIAS BY SEROLOGICAL METHODS. Nature. 1964 Feb 22;201:777–779. doi: 10.1038/201777a0. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Plata F., Langlade-Demoyen P., Abastado J. P., Berbar T., Kourilsky P. Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo. Cell. 1987 Jan 30;48(2):231–240. doi: 10.1016/0092-8674(87)90426-0. [DOI] [PubMed] [Google Scholar]
  34. Plata F., Lilly F. Viral specificity of H-2-restricted T killer cells directed against syngeneic tumors induced by Gross, Friend, or Rauscher leukemia virus. J Exp Med. 1979 Nov 1;150(5):1174–1186. doi: 10.1084/jem.150.5.1174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Plata F. Specificity studies on cytolytic T lymphocytes directed against murine leukemia virus-induced tumors. Analysis of monoclonal cytolytic T lymphocytes. J Exp Med. 1982 Apr 1;155(4):1050–1062. doi: 10.1084/jem.155.4.1050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Robertson M. N., Spangrude G. J., Hasenkrug K., Perry L., Nishio J., Wehrly K., Chesebro B. Role and specificity of T-cell subsets in spontaneous recovery from Friend virus-induced leukemia in mice. J Virol. 1992 Jun;66(6):3271–3277. doi: 10.1128/jvi.66.6.3271-3277.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ruan K. S., Lilly F. Identification of an epitope encoded in the env gene of Friend murine leukemia virus recognized by anti-Friend virus cytotoxic T lymphocytes. Virology. 1991 Mar;181(1):91–100. doi: 10.1016/0042-6822(91)90473-o. [DOI] [PubMed] [Google Scholar]
  38. Rudensky AYu, Preston-Hurlburt P., Hong S. C., Barlow A., Janeway C. A., Jr Sequence analysis of peptides bound to MHC class II molecules. Nature. 1991 Oct 17;353(6345):622–627. doi: 10.1038/353622a0. [DOI] [PubMed] [Google Scholar]
  39. Sanger F. Determination of nucleotide sequences in DNA. Science. 1981 Dec 11;214(4526):1205–1210. doi: 10.1126/science.7302589. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Sitbon M., Sola B., Evans L., Nishio J., Hayes S. F., Nathanson K., Garon C. F., Chesebro B. Hemolytic anemia and erythroleukemia, two distinct pathogenic effects of Friend MuLV: mapping of the effects to different regions of the viral genome. Cell. 1986 Dec 26;47(6):851–859. doi: 10.1016/0092-8674(86)90800-7. [DOI] [PubMed] [Google Scholar]
  42. Smith G. L., Murphy B. R., Moss B. Construction and characterization of an infectious vaccinia virus recombinant that expresses the influenza hemagglutinin gene and induces resistance to influenza virus infection in hamsters. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7155–7159. doi: 10.1073/pnas.80.23.7155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Stukart M. J., Vos A., Boes J., Melvold R. W., Bailey D. W., Melief C. J. A crucial role of the H-2 D locus in the regulation of both the D- and the K-associated cytotoxic T lymphocyte response against Moloney leukemia virus, demonstrated with two Db mutants. J Immunol. 1982 Mar;128(3):1360–1364. [PubMed] [Google Scholar]
  44. Udono H., Mieno M., Shiku H., Nakayama E. The roles of CD8+ and CD4+ cells in tumor rejection. Jpn J Cancer Res. 1989 Jul;80(7):649–654. doi: 10.1111/j.1349-7006.1989.tb01692.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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]
  46. Wolff L., Scolnick E., Ruscetti S. Envelope gene of the Friend spleen focus-forming virus: deletion and insertions in 3' gp70/p15E-encoding region have resulted in unique features in the primary structure of its protein product. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4718–4722. doi: 10.1073/pnas.80.15.4718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yague J., Blackman M., Born W., Marrack P., Kappler J., Palmer E. The structure of V alpha and J alpha segments in the mouse. Nucleic Acids Res. 1988 Dec 9;16(23):11355–11364. doi: 10.1093/nar/16.23.11355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. van der Hoorn F. A., Lahaye T., Müller V., Ogle M. A., Engers H. D. Characterization of gP85gag as an antigen recognized by Moloney leukemia virus-specific cytolytic T cell clones that function in vivo. J Exp Med. 1985 Jul 1;162(1):128–144. doi: 10.1084/jem.162.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES