title: Human CD8(+) T Cells Target Multiple Epitopes in Respiratory Syncytial Virus Polymerase.
abstract: Respiratory syncytial virus (RSV) infection is a serious health problem in young children, immunocompromised patients, and the elderly. The development of novel prevention strategies, such as a vaccine to RSV, is a high priority. One strategy is to design a peptide-based vaccine that activates appropriate CD8(+) T-cell responses. However, this approach is limited by the low number of RSV peptide epitopes defined to date that activate CD8(+) T cells. We aimed to identify peptide epitopes that are presented by common human leukocyte antigen types (HLA-A*01, -A*02, and -B*07). We identify one novel HLA-A*02-restricted and two novel HLA-A*01-restricted peptide epitopes from RSV polymerase. Peptide-HLA multimer staining of specific T cells from healthy donor peripheral blood mononuclear cell, the memory phenotype of such peptide-specific T cells ex vivo, and functional IFNγ responses in short-term stimulation assays suggest that these peptides are recognized during RSV infection. Such peptides are candidates for inclusion into a peptide-based RSV vaccine designed to stimulate defined CD8(+) T-cell responses.
authors.affiliation: 1 Institute for Medical Virology, University Hospital Tübingen , Tübingen, Germany .
authors.forename: Daniel
authors.initials: D
authors.lastname: Burbulla
authors.affiliation: 1 Institute for Medical Virology, University Hospital Tübingen , Tübingen, Germany .
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Günther
authors.affiliation: 2 Department of Immunology, University of Tübingen , Tübingen, Germany .
authors.forename: Janet K
authors.initials: JK
authors.lastname: Peper
authors.affiliation: 1 Institute for Medical Virology, University Hospital Tübingen , Tübingen, Germany .
authors.forename: Gerhard
authors.initials: G
authors.lastname: Jahn
authors.affiliation: 1 Institute for Medical Virology, University Hospital Tübingen , Tübingen, Germany .
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Dennehy
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D045744:Cell Line, Tumor; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D020014:K562 Cells; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000737:chemistry / Q000276:immunology*; D022223:Vaccines, Subunit; D014765:Viral Vaccines / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D015234:HLA-A Antigens; D010455:Peptides; D020033:Protein Isoforms; D022223:Vaccines, Subunit; D014765:Viral Vaccines; D012321:DNA-Directed RNA Polymerases