Human CD8(+) T Cells Target Multiple Epitopes in Respiratory Syncytial Virus Polymerase

Viral Immunol. 2016 Jun;29(5):307-14. doi: 10.1089/vim.2015.0091. Epub 2016 Apr 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Line, Tumor
  • DNA-Directed RNA Polymerases / chemistry
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / immunology*
  • Epitope Mapping
  • Epitopes / chemistry
  • Epitopes / genetics
  • Epitopes / immunology*
  • HLA-A Antigens / chemistry
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology*
  • Humans
  • Immunologic Memory
  • K562 Cells
  • Peptides / chemical synthesis
  • Peptides / genetics
  • Peptides / immunology
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Respiratory Syncytial Virus, Human / chemistry
  • Respiratory Syncytial Virus, Human / immunology*
  • Vaccines, Subunit
  • Viral Vaccines / biosynthesis
  • Viral Vaccines / immunology*

Substances

  • Antigens, Viral
  • Epitopes
  • HLA-A Antigens
  • Peptides
  • Protein Isoforms
  • Vaccines, Subunit
  • Viral Vaccines
  • DNA-Directed RNA Polymerases