PRESENTATION BY A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE OF NUCLEOPROTEIN PEPTIDE EXPRESSED IN 2 DIFFERENT GENES OF AN INFLUENZA-VIRUS TRANSFECTANT

Major histocompatibility (MHC) class I glycoproteins are specialized t o present to CD8(+) T cells, peptides that originate from proteins syn thesized within the cytoplasm. Conventional killed vaccines are unable to get into the cell cytoplasm and therefore fail to expand the CD8() T cell population. We have created a novel influenza transfectant vi rus, R10, which carries an immunogenic peptide from the nucleoprotein (NP) of PR8 influenza virus in its hemagglutinin (HA) and another simi lar peptide in its HK influenza virus NP. The two peptides are both pr esented by H-2D(b) and bind with approximately equal affinity. They ca n compete with one another for binding to H-2D(b). Yet in cells infect ed with R10, both peptides are presented efficiently enough to expand the respective cytotoxic T lymphocyte (CTL) precursors in vivo and to serve as targets for CTL lysis in vitro. It has been proposed that pro teins bearing signal sequences may be processed by a transporter-indep endent pathway. To investigate this, we infected the transporter-defic ient cell line RMA-S with the R10 virus to see if the NP peptide expre ssed by the HA would be presented. The result shows that even the pres ence of a signal peptide in the HA does not overcome the lack of a tra nsporter function, suggesting that the presentation of both peptides i s dependent on functional transporter proteins. Our data also suggest the feasibility of creating by genetic engineering, recombinant vaccin es expressing multiple epitopes that can effectively stimulate a cellu lar immune response.