Unusual viral ligand with alternative interactions is presented by HLA-Cw4 in human respiratory syncytial virus-infected cells.
Short viral antigens bound to human major histocompatibility complex (HLA) class I molecules are presented on infected cells. Vaccine development frequently relies on synthetic peptides to identify optimal HLA class I ligands. However, when natural peptides are analyzed, more complex mixtures are found. By immunoproteomics analysis, we identify in this study a physiologically processed HLA ligand derived from the human respiratory syncytial virus matrix protein that is very different from what was expected from studies with synthetic peptides. This natural HLA-Cw4 class I ligand uses alternative interactions to the anchor motifs previously described for its presenting HLA-Cw4 class I molecule. Finally, this octameric peptide shares its C-terminal core with the H-2D(b) nonamer ligand previously identified in the mouse model. These data have implications for the identification of antiviral cytotoxic T lymphocyte responses and for vaccine development.
Unidad de Procesamiento Antigénico, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Susana
S
Infantes
Elena
E
Lorente
Juan José
JJ
Cragnolini
Manuel
M
Ramos
Ruth
R
García
Mercedes
M
Jiménez
Salvador
S
Iborra
Margarita
M
Del Val
Daniel
D
López
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D015236:HLA-C Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008024:Ligands; D051379:Mice; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*
D000956:Antigens, Viral; D015236:HLA-C Antigens; C039966:HLA-C*04 antigen; D015395:Histocompatibility Antigens Class I; D008024:Ligands; C408902:MHC binding peptide; D009842:Oligopeptides; D010455:Peptides