CD8+ T cells specific for a single nonamer epitope of Listeria monocytogenes are protective in vivo.
Class I major histocompatibility complex (MHC)-restricted CD8+ T cells have been demonstrated to be effective mediators of both acquired and adoptive immunity to the intracellular bacterium Listeria monocytogenes. We have recently determined that L. monocytogenes-infected H-2d mice recognize a nonamer peptide, residues 91-99, of the secreted protein listeriolysin O (LLO), in a H-2Kd-restricted fashion. In this report we have generated CD8+ T cell lines with specificity for LLO 91-99 in the context of H-2Kd by in vitro stimulation with P815 (H-2d) cells transfected with LLO. These CD8+ lines have been generated from immune donors after sublethal infection with L. monocytogenes, or after in vivo immunization with syngeneic spleen cells coated with synthetic LLO 91-99 peptide. LLO-specific CD8+ T cells derived from either protocol were capable of significant protection against L. monocytogenes infection. The in vivo protection by these CD8+ T cell lines has been shown to be solely due to recognition of LLO 91-99 in the context of H-2Kd. These studies demonstrate that CD8+ T cell immunity to a single, naturally produced peptide epitope has the potential for significant protection in a bacterial infection. Thus, the allele-specific motif approach to epitope prediction has identified a naturally produced bacterial epitope with biological relevance.
Harty
J T
JT
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Bevan
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins; D016827:CD8 Antigens / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D006460:Hemolysin Proteins / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007111:Immunity, Cellular; D007700:Kinetics; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016827:CD8 Antigens; D000939:Epitopes; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I; D009842:Oligopeptides; C038705:hlyA protein, Listeria monocytogenes