Use of Synthetic Peptides of Influenza

CTL are partly responsible for the immune response to influenza viruses in both mouse and man . The majority of CTL detectable in vivo and early in polyclonal cultures in vitro, crossreact on target cells infected with all strains of A viruses but not B viruses (1, 2) . This crossreactive CTL response may play a role in the heterotypic protection observed in rodents and man after infection by serologically distinct influenza A strains (3, 4) . The identification of the conserved viral molecules that are recognized by crossreactive CTL has depended on rDNA techniques to express individual viral proteins in cell lines in vitro . In both mice and man the predominant conserved epitopes turn out to be on the nonglycosylated proteins of the virus (5-9). The nucleoprotein (NP)' is a major antigen in H-2k, -d, and -b strains of mice (5, 6) and in the majority of humans (7). PB 1, PB2, PA, NS I , and M I also have been shown to be recognized by class I-restricted CTL (7, 8) . The CTL response to NP appears to be under strict genetic control in both mice and man, responder status being conferred by single polymorphic class I genes in each case (10-12) . Recent efforts (10) to map the epitopes recognized to regions of the NP sequence using deletion mutants of the NP gene have shown that the immunodominant epitopes lie in different regions of the molecule in H-2b and -k strains of mice . These experiments also showed that the recognition of NP by CTL was not dependent on a definable signal sequence in the molecule, and led to the suggestion that NP may be recognized after degradation in the target cell . Further work (13) demonstrated that an epitope mapped to a short region of NP that had undergone genetic change since 1934 could be replaced in vitro with a short peptide (amino acids 366-379) . Two mutually exclusive epitopes were thus defined using CTL clones that differentiated between two groups of A viruses isolated between 1934-1943 and 1946-1968. During the course of these experiments an additional epitope recognized by HLA-B37-restricted human CTL was defined with a second NP peptide (335-349) (13) .