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. 1995 Nov;69(11):6735–6741. doi: 10.1128/jvi.69.11.6735-6741.1995

A single retroviral gag precursor signal peptide recognized by FBL-3 tumor-specific cytotoxic T lymphocytes.

T Kondo 1, H Uenishi 1, T Shimizu 1, T Hirama 1, M Iwashiro 1, K Kuribayashi 1, H Tamamura 1, N Fujii 1, R Fujisawa 1, M Miyazawa 1, et al.
PMCID: PMC189584  PMID: 7474084

Abstract

Several dominant T-cell receptors of cytotoxic T-lymphocyte (CTL) clones specific for FBL-3 tumor antigen were clonally amplified in mixed lymphocyte tumor cell cultures derived from an individual immune mouse. Every CTL clone analyzed had a common specificity for a single epitope in the precursor to cell membrane-associated nonstructural gag-encoded protein, Pr75gag, which can be minimally identified by nine amino acid residues, SIVLCCLCL. This epitope is located within the hydrophobic signal sequence motif that mediates translocation of the protein into the endoplasmic reticulum. These novel observations suggest that expression of Pr75gag in FBL-3 tumor cells led to the amplification of CTLs which recognize the signal sequence of the nonstructural gag-encoded glycoprotein precursor.

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Selected References

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  1. Allen H., Wraith D., Pala P., Askonas B., Flavell R. A. Domain interactions of H-2 class I antigens alter cytotoxic T-cell recognition sites. Nature. 1984 May 17;309(5965):279–281. doi: 10.1038/309279a0. [DOI] [PubMed] [Google Scholar]
  2. Becker D. M., Pattern P., Chien Y., Yokota T., Eshhar Z., Giedlin M., Gascoigne N. R., Goodnow C., Wolf R., Arai K. Variability and repertoire size of T-cell receptor V alpha gene segments. Nature. 1985 Oct 3;317(6036):430–434. doi: 10.1038/317430a0. [DOI] [PubMed] [Google Scholar]
  3. Behlke M. A., Spinella D. G., Chou H. S., Sha W., Hartl D. L., Loh D. Y. T-cell receptor beta-chain expression: dependence on relatively few variable region genes. Science. 1985 Aug 9;229(4713):566–570. doi: 10.1126/science.3875151. [DOI] [PubMed] [Google Scholar]
  4. Bill J., Kanagawa O., Woodland D. L., Palmer E. The MHC molecule I-E is necessary but not sufficient for the clonal deletion of V beta 11-bearing T cells. J Exp Med. 1989 Apr 1;169(4):1405–1419. doi: 10.1084/jem.169.4.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Chien Y. H., Gascoigne N. R., Kavaler J., Lee N. E., Davis M. M. Somatic recombination in a murine T-cell receptor gene. Nature. 1984 May 24;309(5966):322–326. doi: 10.1038/309322a0. [DOI] [PubMed] [Google Scholar]
  7. Corbin A., Prats A. C., Darlix J. L., Sitbon M. A nonstructural gag-encoded glycoprotein precursor is necessary for efficient spreading and pathogenesis of murine leukemia viruses. J Virol. 1994 Jun;68(6):3857–3867. doi: 10.1128/jvi.68.6.3857-3867.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [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. FRIEND C. Cell-free transmission in adult Swiss mice of a disease having the character of a leukemia. J Exp Med. 1957 Apr 1;105(4):307–318. doi: 10.1084/jem.105.4.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Falk K., Rötzschke O., Stevanović S., Jung G., Rammensee H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
  12. Fink P. J., Matis L. A., McElligott D. L., Bookman M., Hedrick S. M. Correlations between T-cell specificity and the structure of the antigen receptor. Nature. 1986 May 15;321(6067):219–226. doi: 10.1038/321219a0. [DOI] [PubMed] [Google Scholar]
  13. Henderson R. A., Michel H., Sakaguchi K., Shabanowitz J., Appella E., Hunt D. F., Engelhard V. H. HLA-A2.1-associated peptides from a mutant cell line: a second pathway of antigen presentation. Science. 1992 Mar 6;255(5049):1264–1266. doi: 10.1126/science.1546329. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Holt C. A., Osorio K., Lilly F. Friend virus-specific cytotoxic T lymphocytes recognize both gag and env gene-encoded specificities. J Exp Med. 1986 Jul 1;164(1):211–226. doi: 10.1084/jem.164.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Iwamoto A., Ohashi P. S., Pircher H., Walker C. L., Michalopoulos E. E., Rupp F., Hengartner H., Mak T. W. T cell receptor variable gene usage in a specific cytotoxic T cell response. Primary structure of the antigen-MHC receptor of four hapten-specific cytotoxic T cell clones. J Exp Med. 1987 Mar 1;165(3):591–600. doi: 10.1084/jem.165.3.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Iwashiro M., Kondo T., Shimizu T., Yamagishi H., Takahashi K., Matsubayashi Y., Masuda T., Otaka A., Fujii N., Ishimoto A. Multiplicity of virus-encoded helper T-cell epitopes expressed on FBL-3 tumor cells. J Virol. 1993 Aug;67(8):4533–4542. doi: 10.1128/jvi.67.8.4533-4542.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jorgensen J. L., Esser U., Fazekas de St Groth B., Reay P. A., Davis M. M. Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics. Nature. 1992 Jan 16;355(6357):224–230. doi: 10.1038/355224a0. [DOI] [PubMed] [Google Scholar]
  19. Kedar E., Weiss D. W. The in vitro generation of effector lymphocytes and their employment in tumor immunotherapy. Adv Cancer Res. 1983;38:171–287. doi: 10.1016/s0065-230x(08)60190-6. [DOI] [PubMed] [Google Scholar]
  20. 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]
  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. Kuribayashi K., Tanaka C., Matsubayashi Y., Masuda T., Udono H., Abe M., Nakayama E., Shiku H. Anti-idiotypic antibodies against UV-induced tumor-specific CTL clones. Preparation in syngeneic combination. J Immunol. 1988 Dec 1;141(11):4074–4080. [PubMed] [Google Scholar]
  23. Malissen M., Minard K., Mjolsness S., Kronenberg M., Goverman J., Hunkapiller T., Prystowsky M. B., Yoshikai Y., Fitch F., Mak T. W. Mouse T cell antigen receptor: structure and organization of constant and joining gene segments encoding the beta polypeptide. Cell. 1984 Jul;37(3):1101–1110. doi: 10.1016/0092-8674(84)90444-6. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. North R. J. Down-regulation of the antitumor immune response. Adv Cancer Res. 1985;45:1–43. doi: 10.1016/s0065-230x(08)60265-1. [DOI] [PubMed] [Google Scholar]
  27. Nowinski R. C., Emery S., Ledbetter J. Identification of an FMR cell surface antigen associated with murine leukemia virus-infected cells. J Virol. 1978 Jun;26(3):805–812. doi: 10.1128/jvi.26.3.805-812.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Payne J., Huber B. T., Cannon N. A., Schneider R., Schilham M. W., Acha-Orbea H., MacDonald H. R., Hengartner H. Two monoclonal rat antibodies with specificity for the beta-chain variable region V beta 6 of the murine T-cell receptor. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7695–7698. doi: 10.1073/pnas.85.20.7695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Peabody D. S. Translation initiation at non-AUG triplets in mammalian cells. J Biol Chem. 1989 Mar 25;264(9):5031–5035. [PubMed] [Google Scholar]
  30. Perryman S., Nishio J., Chesebro B. Complete nucleotide sequence of Friend murine leukemia virus, strain FB29. Nucleic Acids Res. 1991 Dec 25;19(24):6950–6950. doi: 10.1093/nar/19.24.6950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Prats A. C., De Billy G., Wang P., Darlix J. L. CUG initiation codon used for the synthesis of a cell surface antigen coded by the murine leukemia virus. J Mol Biol. 1989 Jan 20;205(2):363–372. doi: 10.1016/0022-2836(89)90347-1. [DOI] [PubMed] [Google Scholar]
  32. Pullen A. M., Marrack P., Kappler J. W. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988 Oct 27;335(6193):796–801. doi: 10.1038/335796a0. [DOI] [PubMed] [Google Scholar]
  33. Robertson M. N., Miyazawa M., Mori S., Caughey B., Evans L. H., Hayes S. F., Chesebro B. Production of monoclonal antibodies reactive with a denatured form of the Friend murine leukemia virus gp70 envelope protein: use in a focal infectivity assay, immunohistochemical studies, electron microscopy and western blotting. J Virol Methods. 1991 Oct;34(3):255–271. doi: 10.1016/0166-0934(91)90105-9. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Ruscetti S., Linemeyer D., Field J., Troxler D., Scolnick E. Type-specific radioimmunoassays for the gp70s of mink cell focus-inducing murine leukemia viruses: expression of a cross-reacting antigen in cells infected with the Friend strain of the spleen focus-forming virus. J Exp Med. 1978 Sep 1;148(3):654–663. doi: 10.1084/jem.148.3.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rötzschke O., Falk K., Deres K., Schild H., Norda M., Metzger J., Jung G., Rammensee H. G. Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature. 1990 Nov 15;348(6298):252–254. doi: 10.1038/348252a0. [DOI] [PubMed] [Google Scholar]
  38. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  39. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature. 1984 Nov 1;312(5989):36–40. doi: 10.1038/312036a0. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Shimizu T., Uenishi H., Teramura Y., Iwashiro M., Kuribayashi K., Tamamura H., Fujii N., Yamagishi H. Fine structure of a virus-encoded helper T-cell epitope expressed on FBL-3 tumor cells. J Virol. 1994 Dec;68(12):7704–7708. doi: 10.1128/jvi.68.12.7704-7708.1994. [DOI] [PMC free article] [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. Siu G., Kronenberg M., Strauss E., Haars R., Mak T. W., Hood L. The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor. 1984 Sep 27-Oct 3Nature. 311(5984):344–350. doi: 10.1038/311344a0. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. Staerz U. D., Rammensee H. G., Benedetto J. D., Bevan M. J. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J Immunol. 1985 Jun;134(6):3994–4000. [PubMed] [Google Scholar]
  46. Steeves R. A. Editorial: Spleen focus-forming virus in Friend and Rauscher leukemia virus preparations. J Natl Cancer Inst. 1975 Feb;54(2):289–297. doi: 10.1093/jnci/54.2.289. [DOI] [PubMed] [Google Scholar]
  47. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  48. Utsunomiya Y., Bill J., Palmer E., Gollob K., Takagaki Y., Kanagawa O. Analysis of a monoclonal rat antibody directed to the alpha-chain variable region (V alpha 3) of the mouse T cell antigen receptor. J Immunol. 1989 Oct 15;143(8):2602–2608. [PubMed] [Google Scholar]
  49. 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]

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