title: Identification of CD8+ T-cell epitopes specific for immediate-early transactivator Rta of Epstein-Barr virus.
abstract: Nasopharyngeal carcinoma (NPC) is a human epithelial tumor with a high incidence in Southern Chinese population, with contributions from Epstein-Barr virus (EBV), human leukocyte antigen (HLA), and environmental factors to its etiology. It has been shown previously that the recognition of immediate-early transactivator Rta of EBV by CD8+ T cells may have a significant impact on controlling EBV and, indirectly, NPC. The current study used two computer-aided prediction methods and competition-based HLA-peptide binding assays to screen for HLA B2704/B4601/B5801 restricted T-cell epitopes derived from Rta. HLA tetrameric complexes containing these potential T-cell epitopes were synthesized. Rta-specific CD8+ T-cell responses in healthy virus carriers were then defined by these tetramers and IFN-gamma ELISPOT assays. We clearly demonstrated that healthy virus carriers have detectable Rta-specific CD8+ T cells restricted by B2704 in the circulation. However, there were no B4601/B5801 tetramer-reactive T cells specific for Rta in the peripheral blood of matched/mismatched donors. On the other hand, B4601 tetramers containing the computer-predicted B4601 binder EBNA3A (318-326) showed detectable tetramer-reactive T cells in the circulation of healthy virus carriers. topes also elicited IFN-gamma responses as detected by ELISPOT.
authors.affiliation: WHO Immunology Centre, Faculty of Medicine, National University of Singapore, Republic of Singapore.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Yu
authors.forename: Nalini
authors.initials: N
authors.lastname: Srinivasan
authors.forename: Eechee
authors.initials: E
authors.lastname: Ren
authors.forename: Sohha
authors.initials: S
authors.lastname: Chan
mesh_terms: D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003198:Computer Simulation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins
chemical_list: C068382:BRLF1 protein, Human herpesvirus 4; D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D015235:HLA-B Antigens; D017874:Immediate-Early Proteins; D010446:Peptide Fragments; D015534:Trans-Activators; D014764:Viral Proteins; D007371:Interferon-gamma