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. 1986 Jun 1;163(6):1529–1538. doi: 10.1084/jem.163.6.1529

Recognition of cloned vesicular stomatitis virus internal and external gene products by cytotoxic T lymphocytes

PMCID: PMC2188125  PMID: 3011949

Abstract

It has generally been assumed that most if not all CTL specific for vesicular stomatitis virus (VSV)-infected cells recognize the viral glycoprotein (G), an integral membrane protein abundantly expressed on infected cell surfaces. Using recombinant vaccinia viruses containing copies of cloned VSV genes to examine CTL recognition of VSV, we have confirmed that G is recognized by VSV-specific CTL. More interestingly, however, we have also found that nucleocapsid protein (N), an internal virion protein, can be detected on infected cell surfaces using mAb, and serves as a major target antigen for VSV-specific CTL. In contrast to the highly serotype-specific recognition of G, N is recognized by a major population of CTL able to lyse cells infected with either the Indiana or New Jersey VSV serotypes. Using target cells expressing a cloned MHC class I gene, we could directly show that CTL recognition of N occurs in the context of the MHC Ld molecule.

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Selected References

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

  1. Bennink J. R., Yewdell J. W., Smith G. L., Moller C., Moss B. Recombinant vaccinia virus primes and stimulates influenza haemagglutinin-specific cytotoxic T cells. Nature. 1984 Oct 11;311(5986):578–579. doi: 10.1038/311578a0. [DOI] [PubMed] [Google Scholar]
  2. Bennink J. R., Yewdell J. W., Smith G. L., Moss B. Recognition of cloned influenza virus hemagglutinin gene products by cytotoxic T lymphocytes. J Virol. 1986 Mar;57(3):786–791. doi: 10.1128/jvi.57.3.786-791.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Braciale T. J., Braciale V. L., Henkel T. J., Sambrook J., Gething M. J. Cytotoxic T lymphocyte recognition of the influenza hemagglutinin gene product expressed by DNA-mediated gene transfer. J Exp Med. 1984 Feb 1;159(2):341–354. doi: 10.1084/jem.159.2.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ciavarra R., Forman J. Cell membrane antigens recognized by anti-viral and anti-trinitrophenyl cytotoxic T lymphocytes. Immunol Rev. 1981;58:73–94. doi: 10.1111/j.1600-065x.1981.tb00350.x. [DOI] [PubMed] [Google Scholar]
  5. Ciavarra R., Forman J. H-2L-restricted recognition of viral antigens In the H-2d haplotype, anti-vesicular stomatitis virus cytotoxic T cells are restricted solely by H-2L. J Exp Med. 1982 Sep 1;156(3):778–790. doi: 10.1084/jem.156.3.778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Doherty P. C., Knowles B. B., Wettstein P. J. Immunological surveillance of tumors in the context of major histocompatibility complex restriction of T cell function. Adv Cancer Res. 1984;42:1–65. doi: 10.1016/s0065-230x(08)60455-8. [DOI] [PubMed] [Google Scholar]
  7. Fleischer B., Becht H., Rott R. Recognition of viral antigens by human influenza A virus-specific T lymphocyte clones. J Immunol. 1985 Oct;135(4):2800–2804. [PubMed] [Google Scholar]
  8. Forman J., Goodenow R. S., Hood L., Ciavarra R. Use of DNA-mediated gene transfer to analyze the role of H-2Ld in controlling the specificity of anti-vesicular stomatitis virus cytotoxic T cells. J Exp Med. 1983 Apr 1;157(4):1261–1272. doi: 10.1084/jem.157.4.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gething M., Koszinowski U., Waterfield M. Fusion of Sendai virus with the target cell membrane is required for T cell cytotoxicity. Nature. 1978 Aug 17;274(5672):689–691. doi: 10.1038/274689a0. [DOI] [PubMed] [Google Scholar]
  10. Gooding L. R., O'Connell K. A. Recognition by cytotoxic T lymphocytes of cells expressing fragments of the SV40 tumor antigen. J Immunol. 1983 Nov;131(5):2580–2586. [PubMed] [Google Scholar]
  11. Gooding L. R. Specificities of killing by cytotoxic lymphocytes generated in vivo and in vitro to syngeneic SV40 transformed cells. J Immunol. 1977 Mar;118(3):920–927. [PubMed] [Google Scholar]
  12. Hale A. H., Witte O. N., Baltimore D., Eisen H. N. Vesicular stomatitis virus glycoprotein is necessary for H-2-restricted lysis of infected cells by cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1978 Feb;75(2):970–974. doi: 10.1073/pnas.75.2.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Henning R., Lange-Mutschler J., Deppert W. SV40-transformed cells express SV40 T antigen-related antigens on the cell surface. Virology. 1981 Jan 30;108(2):325–337. doi: 10.1016/0042-6822(81)90441-4. [DOI] [PubMed] [Google Scholar]
  14. Jacobson S., Richert J. R., Biddison W. E., Satinsky A., Hartzman R. J., McFarland H. F. Measles virus-specific T4+ human cytotoxic T cell clones are restricted by class II HLA antigens. J Immunol. 1984 Aug;133(2):754–757. [PubMed] [Google Scholar]
  15. Kauffman R. S., Lee S., Finberg R. Cytolytic T-cell mediated lysis of reovirus-infected cells: requirements for infectious virus, viral particles, and viral proteins in infected target cells. Virology. 1983 Dec;131(2):265–273. doi: 10.1016/0042-6822(83)90495-6. [DOI] [PubMed] [Google Scholar]
  16. Lefrancios L., Lyles D. S. The interactionof antiody with the major surface glycoprotein of vesicular stomatitis virus. I. Analysis of neutralizing epitopes with monoclonal antibodies. Virology. 1982 Aug;121(1):157–167. [PubMed] [Google Scholar]
  17. Lukacher A. E., Morrison L. A., Braciale V. L., Malissen B., Braciale T. J. Expression of specific cytolytic activity by H-2I region-restricted, influenza virus-specific T lymphocyte clones. J Exp Med. 1985 Jul 1;162(1):171–187. doi: 10.1084/jem.162.1.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mackett M., Yilma T., Rose J. K., Moss B. Vaccinia virus recombinants: expression of VSV genes and protective immunization of mice and cattle. Science. 1985 Jan 25;227(4685):433–435. doi: 10.1126/science.2981435. [DOI] [PubMed] [Google Scholar]
  19. Pala P., Askonas B. A. Induction of Kb-restricted anti-influenza cytotoxic T cells in C57BL mice: importance of stimulator cell type and immunization route. Immunology. 1985 Aug;55(4):601–607. [PMC free article] [PubMed] [Google Scholar]
  20. Pan S., Knowles B. B. Monoclonal antibody to SV40 T-antigen blocks lysis of cloned cytotoxic T-cell line specific for SV40 TASA. Virology. 1983 Feb;125(1):1–7. doi: 10.1016/0042-6822(83)90058-2. [DOI] [PubMed] [Google Scholar]
  21. Rodriguez Boulan E., Sabatini D. D. Asymmetric budding of viruses in epithelial monlayers: a model system for study of epithelial polarity. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5071–5075. doi: 10.1073/pnas.75.10.5071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rosenthal K. L., Zinkernagel R. M. Cross-reactive cytotoxic T cells to serologically distinct vesicular stomatitis virus. J Immunol. 1980 May;124(5):2301–2308. [PubMed] [Google Scholar]
  23. Sethi K. K., Brandis H. The role of vesicular stomatitis virus major glycoprotein in determining the specificity of virus-specific and H-2-restricted cytolytic T cells. Eur J Immunol. 1980 Apr;10(4):268–272. doi: 10.1002/eji.1830100409. [DOI] [PubMed] [Google Scholar]
  24. Sharma S., Rodgers L., Brandsma J., Gething M. J., Sambrook J. SV40 T antigen and the exocytotic pathway. EMBO J. 1985 Jun;4(6):1479–1489. doi: 10.1002/j.1460-2075.1985.tb03806.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tevethia S. S., Flyer D. C., Tjian R. Biology of simian virus 40 (SV40) transplantation antigen (TrAg). VI. Mechanism of induction of SV40 transplantation immunity in mice by purified SV40 T antigen (D2 protein). Virology. 1980 Nov;107(1):13–23. doi: 10.1016/0042-6822(80)90268-8. [DOI] [PubMed] [Google Scholar]
  26. Tevethia S. S., Tevethia M. J., Lewis A. J., Reddy V. B., Weissman S. M. Biology of simian virus 40 (SV40) transplantation antigen (TrAg). IX. Analysis of TrAg in mouse cells synthesizing truncated SV40 large T antigen. Virology. 1983 Jul 30;128(2):319–330. doi: 10.1016/0042-6822(83)90259-3. [DOI] [PubMed] [Google Scholar]
  27. Townsend A. R., Gotch F. M., Davey J. Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell. 1985 Sep;42(2):457–467. doi: 10.1016/0092-8674(85)90103-5. [DOI] [PubMed] [Google Scholar]
  28. Townsend A. R., McMichael A. J., Carter N. P., Huddleston J. A., Brownlee G. G. Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells. Cell. 1984 Nov;39(1):13–25. doi: 10.1016/0092-8674(84)90187-9. [DOI] [PubMed] [Google Scholar]
  29. Weis J. H., Seidman J. G. The expression of major histocompatibility antigens under metallothionein gene promoter control. J Immunol. 1985 Mar;134(3):1999–2003. [PubMed] [Google Scholar]
  30. Yamada A., Young J. F., Ennis F. A. Influenza virus subtype-specific cytotoxic T lymphocytes lyse target cells coated with a protein produced in E. coli. J Exp Med. 1985 Nov 1;162(5):1720–1725. doi: 10.1084/jem.162.5.1720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yasukawa M., Zarling J. M. Human cytotoxic T cell clones directed against herpes simplex virus-infected cells. I. Lysis restricted by HLA class II MB and DR antigens. J Immunol. 1984 Jul;133(1):422–427. [PubMed] [Google Scholar]
  32. Yewdell J. W., Bennink J. R., Smith G. L., Moss B. Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1785–1789. doi: 10.1073/pnas.82.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yewdell J. W., Frank E., Gerhard W. Expression of influenza A virus internal antigens on the surface of infected P815 cells. J Immunol. 1981 May;126(5):1814–1819. [PubMed] [Google Scholar]
  34. Zinkernagel R. M., Althage A., Holland J. Target antigens for H-2-restricted vesicular stomatitis virus-specific cytotoxic T cells. J Immunol. 1978 Aug;121(2):744–748. [PubMed] [Google Scholar]
  35. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

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