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.
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D003429:Cross Reactions; D005814:Genes, Viral; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D011995:Recombination, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D014764:Viral Proteins / Q000276:immunology*; D015678:Viral Structural Proteins
D000956:Antigens, Viral; D014764:Viral Proteins; D015678:Viral Structural Proteins