title: Human CD4 T cell epitopes selective for Vaccinia versus Variola virus.
abstract: Due to the high degree of sequence identity between Orthopoxvirus species, the specific B and T cell responses raised against these viruses are largely cross-reactive and poorly selective. We therefore searched for CD4 T cell epitopes present in the conserved parts of the Vaccinia genome (VACV) but absent from Variola viruses (VARV), with a view to identifying immunogenic sequences selective for VACV. We identified three long peptide fragments from the B7R, B10R and E7R proteins by in silico comparisons of the poxvirus genomes, and evaluated the recognition of these fragments by VACV-specific T cell lines derived from healthy donors. For the 12 CD4 T cell epitopes identified, we assessed their binding to common HLA-DR allotypes and their capacity to induce peptide-specific CD4 T-cell lines. Four peptides from B7R and B10R displayed a broad binding specificity for HLA-DR molecules and induced multiple T cell lines from healthy donors. Besides their absence from VARV, the two B10R peptide sequences were mutated in the Cowpox virus and completely absent from the Monkeypox genome. This work contributes to the development of differential diagnosis of poxvirus infections.
authors.affiliation: CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines, Labex LERMIT, Labex VRI, Gif Sur Yvette F-91191, France.
authors.forename: Alicia
authors.initials: A
authors.lastname: Probst
authors.forename: Aurore
authors.initials: A
authors.lastname: Besse
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Favry
authors.forename: Gilles
authors.initials: G
authors.lastname: Imbert
authors.forename: Valérie
authors.initials: V
authors.lastname: Tanchou
authors.forename: Florence Anne
authors.initials: FA
authors.lastname: Castelli
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillere
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D002460:Cell Line; D003198:Computer Simulation; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D016679:Genome, Viral; D006684:HLA-DR Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D012901:Variola virus / Q000235:genetics* / Q000276:immunology
chemical_list: D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens