Epitopes described in "Protection against lethal viral infection by vaccination with nonimmunodominant peptides."

Article Authors:M Oukka; J C Manuguerra; N Livaditis; S Tourdot; N Riche; I Vergnon; P Cordopatis; K Kosmatopoulos
Article Title:Protection against lethal viral infection by vaccination with nonimmunodominant peptides.
Reference Detail
Reference ID:1000335
Abstract:CTL response of H-2b mice to influenza PR8 virus is directed against the nucleoprotein (NP)-derived immunodominant 366-374 (NP366PR8) peptide presented by the Db molecule. However, NP has three nonimmunodominant peptides corresponding to the 17-25 (NP17), 55-63 (NP55), and 97-105 (NP97) sequences that have the Db consensus motifs and bind to the Db molecule with an intermediate (NP55) or low (NP17 and NP97) affinity. In a previous report, we have shown that NP55 peptide is naturally processed by infected cells. In the present work, we studied whether nonimmunodominant peptides can protect mice against viral infection. Antiviral protection was evaluated by measuring three parameters: survival after inoculation of a lethal dose of mouse-adapted PR8 virus, percentage of pulmonary lesions in surviving mice, and virus clearance from lungs of infected mice. Our results showed that immunization of B6 mice with nonimmunodominant peptides protected from PR8 virus infection, although less efficiently than immunization with the immunodominant NP366PR8 peptide. Protection was mediated by CD8 T cells. The efficacy of nonimmunodominant peptides correlated with their Db binding affinity; the low affinity binders NP17 and NP97 induced a weaker protection than the intermediate affinity binder NP55. A mixture of NP366PR8 and nonimmunodominant peptides gave a higher protection than NP366PR8 peptide alone. In conclusion, nonimmunodominant peptides protect against a viral infection with an efficacy that is proportional to their affinity for the restricting class I molecule.
Affiliations:INSERM Unit 267, Villejuif, France.
Reference Type:Literature
PubMed ID:8816413
Journal:J Immunol
Journal Volume:157
Article Pages:3039-45
Journal ISSN:0022-1767
Article Chemical List:Antigens, Viral;H-2 Antigens;Immunodominant Epitopes;Influenza Vaccines;NP protein, Influenza A virus;Nucleoproteins;Peptide Fragments;RNA-Binding Proteins;Viral Core Proteins
Article MeSH List:Amino Acid Sequence; Animals; Antigens, Viral(immunology); Consensus Sequence; Crosses, Genetic; H-2 Antigens(immunology); Immunodominant Epitopes(immunology); Influenza A virus(immunology); Influenza Vaccines(immunology); Lung(virology); Lymphocyte Depletion; Lymphoma(pathology); Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Nucleoproteins(immunology); Peptide Fragments(immunology); RNA-Binding Proteins; T-Lymphocyte Subsets(immunology); T-Lymphocytes, Cytotoxic(immunology); Tumor Cells, Cultured; Vaccination; Viral Core Proteins(immunology)
Curation Last Updated:2016-01-08 20:10:31