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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Mar;82(6):1785–1789. doi: 10.1073/pnas.82.6.1785

Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes.

J W Yewdell, J R Bennink, G L Smith, B Moss
PMCID: PMC397357  PMID: 3872457

Abstract

Influenza A virus-specific cytotoxic T lymphocytes (CTL) capable of lysing cells infected with any influenza A virus ("cross-reactive CTL") constitute a major portion of the host CTL response to influenza. The viral nucleoprotein (NP), a major internal virion structural protein, has been implicated as a possible target antigen for cross-reactive CTL. To directly examine CTL recognition of NP, a vaccinia virus recombinant containing a DNA copy of an influenza A virus NP gene was constructed. We found that murine cells infected with this virus were efficiently lysed in a major histocompatibility complex-restricted manner by cross-reactive CTL populations obtained by immunization with a variety of influenza A virus subtypes. In addition, the recombinant vaccinia virus containing the PR8 NP gene was able to both stimulate and prime for a vigorous secondary cross-reactive CTL response. Significantly, splenocytes from mice primed by inoculation with the recombinant vaccinia virus containing the PR8 NP gene could be stimulated by influenza A viruses of all three major human subtypes. Finally, unlabeled target competition experiments suggest that NP is a major, but not the sole, viral target antigen recognized by cross-reactive CTL.

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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., Gerhard W. A viral polymerase involved in recognition of influenza virus-infected cells by a cytotoxic T-cell clone. Nature. 1982 Mar 4;296(5852):75–76. doi: 10.1038/296075a0. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Biddison W. E., Doherty P. C., Webster R. G. Antibody to influenza virus matrix protein detects a common antigen on the surface of cells infected with type A influenza viruses. J Exp Med. 1977 Sep 1;146(3):690–697. doi: 10.1084/jem.146.3.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Biddison W. E., Shaw S., Nelson D. L. Virus specificity of human influenza virus-immune cytotoxic T cells. J Immunol. 1979 Feb;122(2):660–664. [PubMed] [Google Scholar]
  5. 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]
  6. Braciale T. J. Immunologic recognition of influenza virus-infected cells. II. Expression of influenza A matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic T cells. J Exp Med. 1977 Sep 1;146(3):673–689. doi: 10.1084/jem.146.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Deppert W., Henning R. SV40 T-antigen-related molecules on the surfaces of HeLa cells infected with adenovirus-2-SV40 hybrids and on SV40-transformed cells. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):225–234. doi: 10.1101/sqb.1980.044.01.026. [DOI] [PubMed] [Google Scholar]
  9. Effros R. B., Doherty P. C., Gerhard W., Bennink J. Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses. J Exp Med. 1977 Mar 1;145(3):557–568. doi: 10.1084/jem.145.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hackett C. J., Askonas B. A., Webster R. G., van Wyke K. Quantitation of influenza virus antigens on infected target cells and their recognition by cross-reactive cytotoxic T cells. J Exp Med. 1980 May 1;151(5):1014–1025. doi: 10.1084/jem.151.5.1014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kees U., Krammer P. H. Most influenza A virus-specific memory cytotoxic T lymphocytes react with antigenic epitopes associated with internal virus determinants. J Exp Med. 1984 Feb 1;159(2):365–377. doi: 10.1084/jem.159.2.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Mackett M., Smith G. L., Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. J Virol. 1984 Mar;49(3):857–864. doi: 10.1128/jvi.49.3.857-864.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McMichael A. J., Askonas B. A. Influenza virus-specific cytotoxic T cells in man; induction and properties of the cytotoxic cell. Eur J Immunol. 1978 Oct;8(10):705–711. doi: 10.1002/eji.1830081007. [DOI] [PubMed] [Google Scholar]
  15. McMichael A. J., Gotch F. M., Noble G. R., Beare P. A. Cytotoxic T-cell immunity to influenza. N Engl J Med. 1983 Jul 7;309(1):13–17. doi: 10.1056/NEJM198307073090103. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Shaw M. W., Lamon E. W., Compans R. W. Surface expression of a nonstructural antigen on influenza A virus-infected cells. Infect Immun. 1981 Dec;34(3):1065–1067. doi: 10.1128/iai.34.3.1065-1067.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Smith G. L., Mackett M., Moss B. Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen. Nature. 1983 Apr 7;302(5908):490–495. doi: 10.1038/302490a0. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Soule H. R., Butel J. S. Subcellular Localization of simian virus 40 large tumor antigen. J Virol. 1979 May;30(2):523–532. doi: 10.1128/jvi.30.2.523-532.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Townsend A. R., Skehel J. J., Taylor P. M., Palese P. Recognition of influenza A virus nucleoprotein by an H-2-restricted cytotoxic T-cell clone. Virology. 1984 Mar;133(2):456–459. doi: 10.1016/0042-6822(84)90413-6. [DOI] [PubMed] [Google Scholar]
  23. Townsend A. R., Skehel J. J. The influenza A virus nucleoprotein gene controls the induction of both subtype specific and cross-reactive cytotoxic T cells. J Exp Med. 1984 Aug 1;160(2):552–563. doi: 10.1084/jem.160.2.552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Virelizier J. L., Allison A. C., Oxford J. S., Schild G. C. Early presence of ribonucleoprotein antigen on surface of influenza virus-infected cells. Nature. 1977 Mar 3;266(5597):52–54. doi: 10.1038/266052a0. [DOI] [PubMed] [Google Scholar]
  25. Yap K. L., Ada G. L. Cytotoxic T cells specific for influenza virus-infected target cells. Immunology. 1977 Feb;32(2):151–159. [PMC free article] [PubMed] [Google Scholar]
  26. Yap K. L., Ada G. L., McKenzie I. F. Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature. 1978 May 18;273(5659):238–239. doi: 10.1038/273238a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Zweerink H. J., Courtneidge S. A., Skehel J. J., Crumpton M. J., Askonas B. A. Cytotoxic T cells kill influenza virus infected cells but do not distinguish between serologically distinct type A viruses. Nature. 1977 May 26;267(5609):354–356. doi: 10.1038/267354a0. [DOI] [PubMed] [Google Scholar]

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