title: Existing antilisterial immunity does not inhibit the development of a Listeria monocytogenes-specific primary cytotoxic T-lymphocyte response.
abstract: Infection of BALB/c mice with Listeria monocytogenes stimulates an antilisterial immune response evident by the appearance of H2-Kd-restricted CD8(+) cytotoxic T lymphocytes (CTLs) specific for the nanomer peptides amino acids (aa) 91 to 99 of listeriolysin O (LLO 91-99) and aa 217 to 225 of the p60 molecule (p60 217-225). We have introduced point mutations at anchor residues within LLO 91-99 (92F) or p60 217-225 (218F), and BALB/c mice infected with L. monocytogenes strains containing these point mutations do not develop CTLs specific for LLO 91-99 or p60 217-225, respectively. We have used these strains to test whether primary CTL responses against L. monocytogenes-derived determinants can be stimulated within an environment of existing antilisterial immunity. We found that the development of a primary L. monocytogenes-specific CTL response is not altered by existing immunity to L. monocytogenes. For example, primary immunization with the p60 218F strain of L. monocytogenes followed by a secondary immunization with wild-type L. monocytogenes results in stimulation of p60 217-225-specific CTLs at primary response levels and LLO 91-99-specific effectors at levels consistent with a memory CTL response. Similarly, primary immunization with the 92F strain of L. monocytogenes followed by a secondary immunization with wild-type L. monocytogenes results in stimulation of LLO 91-99-specific CTLs at primary response levels and p60 217-225-specific effectors at levels consistent with a memory CTL response. These results provide additional support for the use of L. monocytogenes as a recombinant vaccine vector and show that antivector immunity does not inhibit the development of a primary CTL response when the epitope is delivered by L. monocytogenes as the vaccine strain.
authors.affiliation: Immunology Research, Veterans Affairs Medical Center, Earle A. Chiles Research Institute, Portland, Oregon, USA. bouwera@ohsu.edu
authors.forename: H G
authors.initials: HG
authors.lastname: Bouwer
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.forename: J F
authors.initials: JF
authors.lastname: Miller
authors.forename: R A
authors.initials: RA
authors.lastname: Barry
authors.forename: D J
authors.initials: DJ
authors.lastname: Hinrichs
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001427:Bacterial Toxins; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006460:Hemolysin Proteins; D007110:Immunity, Active / Q000235:genetics; D007111:Immunity, Cellular / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010649:Phenylalanine / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000382:microbiology*
chemical_list: D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D010446:Peptide Fragments; D010649:Phenylalanine; C038705:hlyA protein, Listeria monocytogenes