Class I H-2d-restricted cytotoxic T lymphocytes recognize the neuraminidase glycoprotein of influenza virus subtype N1

Abstract

Class I major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL) that recognize the neuraminidase (NA) glycoprotein of subtype N1 influenza A viruses have been demonstrated in BALB/c mice. Responses to NA were obtained only in protocols that use two in vivo inoculations of virus, including a recombinant vaccinia virus containing the NA of subtype N1 influenza virus (NA-VAC) to prime or boost. Restimulation in vitro was also required for CTL recognition of NA and strongly depended on the specific N1 virus used. Influenza viruses A/Puerto Rico/8/34 (H1N1), A/CAM/46 (H1N1), J1 (H3N1), and JAP/BEL (H2N1), but not A/Bellamy (H1N1) or MEM/BEL (H3N1) virus, were able to stimulate NA-specific memory T cells in vitro. Single or double in vivo inoculation of any of the N1 viruses or a single injection of NA-VAC failed to elicit restimulatable NA-specific CTL. Lysis of NA-VAC-infected cells at low effector/target ratios was comparable to that observed toward other influenza virus proteins known to be major targets of CTL in BALB/c mice, indicating that antigenic determinants of the subtype N1 NA molecule can be efficiently presented in the context of major histocompatibility complex class I.