1. Human CD8(+) T Cells Target Multiple Epitopes in Respiratory Syncytial Virus Polymerase.
- Author
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Burbulla D, Günther PS, Peper JK, Jahn G, and Dennehy KM
- Subjects
- Amino Acid Sequence, Antigen Presentation, Antigens, Viral chemistry, CD8-Positive T-Lymphocytes virology, Cell Line, Tumor, DNA-Directed RNA Polymerases chemistry, DNA-Directed RNA Polymerases genetics, Epitope Mapping, Epitopes chemistry, Epitopes genetics, HLA-A Antigens chemistry, HLA-A Antigens genetics, 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, Vaccines, Subunit, Viral Vaccines biosynthesis, Antigens, Viral immunology, CD8-Positive T-Lymphocytes immunology, DNA-Directed RNA Polymerases immunology, Epitopes immunology, HLA-A Antigens immunology, Respiratory Syncytial Virus, Human immunology, Viral Vaccines immunology
- 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.
- Published
- 2016
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