Sustained CD8+ T-cell immune response to a novel immunodominant HLA-B*0702-associated epitope derived from an Epstein-Barr virus helicase-primase-associated protein.
Generation of a peptide-based vaccine against persistent viral infections, such as Epstein-Barr virus (EBV), requires identification of immunodominant epitopes recognized by anti-viral cytotoxic T-cells. Using available computer algorithms, we have screened the entire translated EBV genome for potential HLA-B7-binding peptides. The binding to HLA-B7 of 18 selected peptides was assessed by competitive binding assays and was found to correlate with the computer-assigned scores, confirming the predictive value of these algorithms in selection of HLA-B7-associated peptides. Screening of the immune responses to these peptides by ELISpot assays identified a novel immunodominant epitope, termed LPRA, derived from an EBV helicase-primase-associated protein encoded by BBLF2/3. Peptide-specific cells constituted up to 0.8% LPRA-specific CD8+ T-cells in the matured anti-viral response. Cytotoxic and proliferative cytotoxic T lymphocytes (CTL) responses to the LPRA peptide were readily demonstrated ex vivo. In addition, mutational studies of this epitope demonstrated a highly specific recognition by LPRA-specific CD8+ T-cells. Taken together, our data suggest that the novel lytic-phase HLA-B7-associated epitope contains essential features required of a component in an EBV peptide-based vaccine.
Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus C, Denmark.
Vanda
V
Turcanová
Per
P
Höllsberg
D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004265:DNA Helicases / Q000235:genetics / Q000276:immunology; D019915:DNA Primase / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology*; D015793:HLA-B7 Antigen; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology* / Q000302:isolation & purification; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D015235:HLA-B Antigens; C477444:HLA-B*07:02 antigen; D015793:HLA-B7 Antigen; D016056:Immunodominant Epitopes; D008024:Ligands; D010455:Peptides; D007371:Interferon-gamma; D019915:DNA Primase; D004265:DNA Helicases