title: A11 Tetramer-assisted characterization of Rta-specific CD8+ T-cell responses in healthy virus carriers.
abstract: HLA Class I-restricted CD8(+) T-cell responses are believed to play an important role in controlling Epstein-Barr virus (EBV) infection, which has been consistently associated with nasopharyngeal carcinoma (NPC). Immediate early transactivator Rta of EBV has been shown to be associated with the reactivation of EBV from latency and drive the lytic cascade of EBV and comprise an important target for EBV-specific cellular cytotoxicity. Furthermore, BRLF1 is specifically expressed in NPC tumor cells. The protein product of BRLF1, Rta, could then be considered as a NPC tumor antigen. Therefore, cellular immunity against Rta represents a very important part of the immunity against NPC, as they should prevent the replication of EBV. In the present study, Rta-specific CD8(+) T-cell responses in healthy virus carriers were characterized by using A1101 tetramer containing the known Rta epitope ATIGTAMYK (134-142). We clearly showed A1101/ATIGTAMYK tetramer-reactive CD8(+) T cells in the circulation of healthy virus carriers, ranging from 2.13 to 9.03%. We then studied the expression of perforin and interferon-gamma (IFN-gamma) secretion in these Rta-specific T cells. Our study demonstrated that Rta-specific T cells are capable of IFN-gamma production and nearly 90% of the Rta-specific CD8(+) T cells expressed perforin. Presumably, these are the cells that play an important role in determining the initiation of the lytic cycle or the clearance of EBV.
authors.affiliation: WHO Immunology Center, Faculty of Medicine, National University of Singapore, Republic of Singapore.
authors.forename: H X
authors.initials: HX
authors.lastname: Yu
authors.forename: N
authors.initials: N
authors.lastname: Srinivasan
authors.forename: E E
authors.initials: EE
authors.lastname: Ren
authors.forename: S H
authors.initials: SH
authors.lastname: Chan
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002353:Carrier State / Q000276:immunology*; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry; D015234:HLA-A Antigens / Q000276:immunology*; D059870:HLA-A11 Antigen; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; C068382:BRLF1 protein, Human herpesvirus 4; D016827:CD8 Antigens; D000939:Epitopes; D006680:HLA Antigens; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D010455:Peptides; D052899:Pore Forming Cytotoxic Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D054353:Perforin; D007371:Interferon-gamma