Immunogenic Peptides of Influenza Virus Subtype Ni Neuraminidase Identify a T-Cell Determinant Used in Class II Major Histocompatibility Complex- Restricted Responses to Infectious Virus

Six nonoverlapping peptides of the neuraminidase (NA) glycoprotein of influenza virus A/Puerto Rico/8/34 (HlNl) (PR8 virus) were found to be immunogenic for proliferating T cells when injected into BALB/c mice in Freund adjuvant. T cells elicited by peptide immunization could recognize PR8 virus in vitro. However, only one of these peptides, corresponding to residues 79 to 93 of NA (NA 79-93), was able to restimulate T cells of mice immunized with infectious virus. T cells that recognized this peptide were uniformly I-Ed restricted, yet infectious influenza virus was required for responses. NA 79-93-specific T-hybridoma clones raised by immunization either with whole virus or with the synthetic peptide alone each responded to replicative virus and not to UV-inactivated virions. These data suggest that the NA 79-93 T-cell determinant which is commonly presented during an encounter with influenza virus in vivo is processed preferentially from NA synthesized within antigen-presenting cells. The neuraminidase (NA) molecule of type A influenza viruses is a glycoprotein of the virion envelope which, along with the hemagglutinin (HA), is a major target of antiviral immune responses. Like HA, the NA molecule is subject to antigenic shift and drift variation (1, 2, 23), with huma