Multiple, non-conserved, internal viral ligands naturally presented by HLA-B27 in human respiratory syncytial virus-infected cells.
Cytotoxic T lymphocyte (CTL)-mediated death of virus-infected cells requires prior recognition of short viral peptide antigens that are presented by human leukocyte antigen (HLA) class I molecules on the surface of infected cells. The CTL response is critical for the clearance of human respiratory syncytial virus (HRSV) infection. Using mass spectrometry analysis of complex HLA-bound peptide pools isolated from large amounts of HRSV-infected cells, we identified nine naturally processed HLA-B27 ligands. The isolated peptides are derived from six internal, not envelope, proteins of the infective virus. The sequences of most of these ligands are not conserved between different HRSV strains, suggesting a mechanism to explain recurrent infection with virus of different HRSV antigenic subgroups. In addition, these nine ligands represent a significant fraction of the proteome of this virus, which is monitored by the same HLA class I allele. These data have implications for vaccine development as well as for analysis of the CTL response.
Infantes
Susana
S
Unidad de Protemica, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain.
Lorente
Elena
E
Barnea
Eilon
E
Beer
Ilan
I
Cragnolini
Juan José
JJ
García
Ruth
R
Lasala
Fátima
F
Jiménez
Mercedes
M
Admon
Arie
A
López
Daniel
D
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides