INDUCTION AND PERSISTENCE OF A CYTOTOXIC T-LYMPHOCYTE (CTL) RESPONSE AGAINST A HERPES-SIMPLEX VIRUS-SPECIFIC CTL EPITOPE EXPRESSED IN A CELLULAR PROTEIN

CD8(+) cytotoxic T-lymphocytes recognize small epitope peptides in ass ociation with MHC class I molecules expressed on the cell surface. In this study, we have determined whether an 8 amino acid viral CTL epito pe, when expressed in a cellular protein, can be appropriately process ed, presented, and recognized by the corresponding epitope-specific CT L and whether it is capable of inducing a CTL response in vivo. An H-2 K(b)-restricted CTL epitope from herpes simplex virus type 1 (HSV-1) g lycoprotein B (gB epitope, residues 498-505) was cloned into the mouse dihydrofolate reductase protein (DHFR) at amino acid position 87. The recombinant DHFRs were expressed in vaccinia virus recombinants. To d istinguish the recombinant DHFR proteins from the endogenous DHFR, an antibody epitope, recognized by monoclonal antibody PAb 901 and derive d from simian virus 40 (SV40) T antigen was tagged to the C-termini of recombinant DHFR proteins. In vivo expression of recombinant DHFR was demonstrated by immunoprecipitation with the monoclonal antibody PAb 901. The H-2(b) cells infected with recombinant vaccinia virus express ing the recombinant DHFR were specifically lysed by gB epitope-specifi c CTL. Furthermore, the recombinant DHFR was functional in inducing a long lasting HSV gB epitope-specific CTL response upon immunization of C57BL/6 (B6) mice. These results indicate that a viral epitope expres sed in a cellular protein can be efficiently processed, presented, and recognized by epitope-specific CTL and show that cellular proteins ex pressing CTL epitopes can be used for induction of CD8(+) T lymphocyte responses. (C) 1996 Academic Press, Inc.