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Proc Natl Acad Sci U S A. 1985 Mar; 82(6): 1785–1789.
PMCID: PMC397357

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


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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  • Yap KL, Ada GL, McKenzie IF. Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature. 1978 May 18;273(5659):238–239. [PubMed]
  • Lin YL, Askonas BA. 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. [PMC free article] [PubMed]
  • Byrne JA, Oldstone MB. Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo. J Virol. 1984 Sep;51(3):682–686. [PMC free article] [PubMed]
  • Effros RB, Doherty PC, 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. [PMC free article] [PubMed]
  • Yap KL, Ada GL. Cytotoxic T cells specific for influenza virus-infected target cells. Immunology. 1977 Feb;32(2):151–159. [PMC free article] [PubMed]
  • Zweerink HJ, Courtneidge SA, Skehel JJ, Crumpton MJ, Askonas BA. 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. [PubMed]
  • McMichael AJ, Askonas BA. Influenza virus-specific cytotoxic T cells in man; induction and properties of the cytotoxic cell. Eur J Immunol. 1978 Oct;8(10):705–711. [PubMed]
  • Biddison WE, Shaw S, Nelson DL. Virus specificity of human influenza virus-immune cytotoxic T cells. J Immunol. 1979 Feb;122(2):660–664. [PubMed]
  • Kees U, Krammer PH. 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. [PMC free article] [PubMed]
  • Braciale TJ, Braciale VL, Henkel TJ, Sambrook J, Gething MJ. 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. [PMC free article] [PubMed]
  • Virelizier JL, Allison AC, Oxford JS, Schild GC. Early presence of ribonucleoprotein antigen on surface of influenza virus-infected cells. Nature. 1977 Mar 3;266(5597):52–54. [PubMed]
  • Yewdell JW, 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]
  • Braciale TJ. 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. [PMC free article] [PubMed]
  • Biddison WE, Doherty PC, Webster RG. 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. [PMC free article] [PubMed]
  • Hackett CJ, Askonas BA, Webster RG, 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. [PMC free article] [PubMed]
  • Shaw MW, Lamon EW, Compans RW. Surface expression of a nonstructural antigen on influenza A virus-infected cells. Infect Immun. 1981 Dec;34(3):1065–1067. [PMC free article] [PubMed]
  • Bennink JR, Yewdell JW, 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. [PubMed]
  • Smith GL, Murphy BR, 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. [PMC free article] [PubMed]
  • Bennink JR, Yewdell JW, Smith GL, Moller C, Moss B. Recombinant vaccinia virus primes and stimulates influenza haemagglutinin-specific cytotoxic T cells. Nature. 1984 Oct 11;311(5986):578–579. [PubMed]
  • Smith GL, Mackett M, Moss B. Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen. Nature. 1983 Apr 7;302(5908):490–495. [PubMed]
  • Mackett M, Smith GL, Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. J Virol. 1984 Mar;49(3):857–864. [PMC free article] [PubMed]
  • Townsend AR, Skehel JJ, Taylor PM, Palese P. Recognition of influenza A virus nucleoprotein by an H-2-restricted cytotoxic T-cell clone. Virology. 1984 Mar;133(2):456–459. [PubMed]
  • Townsend AR, Skehel JJ. 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. [PMC free article] [PubMed]
  • McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med. 1983 Jul 7;309(1):13–17. [PubMed]
  • Soule HR, Butel JS. Subcellular Localization of simian virus 40 large tumor antigen. J Virol. 1979 May;30(2):523–532. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Pan S, Knowles BB. 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. [PubMed]
  • Townsend AR, McMichael AJ, Carter NP, Huddleston JA, Brownlee GG. Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells. Cell. 1984 Nov;39(1):13–25. [PubMed]

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