title: Murine cytotoxic T lymphocytes recognize an epitope in an EBNA-1 fragment, but fail to lyse EBNA-1-expressing mouse cells.
abstract: Major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTLs) specific for epitopes within eight of the nine Epstein Barr Virus (EBV)-encoded latency-associated proteins have been recovered from EBV-infected human subjects by restimulation of lymphocytes in vitro. However, human class I-restricted CTL responses capable of recognizing EBNA-1 expressing cells were not detected in these studies. We have raised a murine CTL line that recognizes an epitope within EBNA-1 by immunizing mice with a vaccinia virus encoding a COOH-terminal EBNA-1 fragment. This novel CTL line was used to investigate whether the epitope (positions 509-517 in EBNA-1, presented through Kd) was presented to CTL by mouse cells expressing full-length EBNA-1 or a deletion mutant of EBNA-1, lacking the Glycine-Alanine (Gly-Ala)-rich region. Cells expressing full-length EBNA-1 are not lysed by the CTL line, whereas cells expressing the Gly-Ala deletion mutant are recognized. These results suggest that epitopes from full-length EBNA-1 are poorly presented, and that the Gly-Ala-rich region is responsible for this phenomenon. The inefficient presentation of EBNA-1-derived epitopes may explain the absence or rarity of EBNA-1-specific CTLs in vivo, a strategy that may allow EBV to maintain persistence within the immunocompetent host without being eliminated by CTLs.
authors.affiliation: Molecular Immunology Group, Institute for Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX39DU, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Mukherjee
authors.forename: P
authors.initials: P
authors.lastname: Trivedi
authors.forename: D M
authors.initials: DM
authors.lastname: Dorfman
authors.forename: G
authors.initials: G
authors.lastname: Klein
authors.forename: A
authors.initials: A
authors.lastname: Townsend
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D002857:Chromium / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000737:chemistry* / Q000276:immunology; D007150:Immunohistochemistry; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000939:Epitopes; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014764:Viral Proteins; D002857:Chromium