title: Epstein-Barr virus isolates with the major HLA B35.01-restricted cytotoxic T lymphocyte epitope are prevalent in a highly B35.01-positive African population.
abstract: An influence of cytotoxic T lymphocyte (CTL) response over Epstein-Barr virus (EBV) evolution was first suggested by the finding that virus isolates from highly HLA-A11-positive Oriental populations were specifically mutated in two immunodominant A11-restricted CTL epitopes. Here we turn to a second HLA allele, B35.01 and show that B35.01-restricted CTL responses in Caucasian donors reproducibly map to a single peptide epitope, YPLHEQHGM, representing residues 458-466 of the type 1 EBV nuclear antigen 3A protein (B95.8 strain). In this case, however, most EBV isolates from a highly B35.01-positive population (in The Gambia) either retained the CTL epitope sequence or carried a mutation (P-->S at position 2) which conserved antigenicity; changes leading to reduced antigenicity (Y-->N at position 1) were found in only a minority of cases. Furthermore, CTL recognizing the YPLHEQHGM epitope could be reactivated from the blood of some B35.01-positive Gambian donors by in vitro stimulation with the synthetic peptide, indicating that epitope-specific immunity does exist in this population. Possible differences between the A11-based and B35.01-based studies are discussed.
authors.affiliation: Institute for Cancer Studies, University of Birmingham, GB.
authors.forename: S P
authors.initials: SP
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Morgan
authors.forename: J
authors.initials: J
authors.lastname: Skinner
authors.forename: W A
authors.initials: WA
authors.lastname: Thomas
authors.forename: S R
authors.initials: SR
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Sutton
authors.forename: R
authors.initials: R
authors.lastname: Khanna
authors.forename: H C
authors.initials: HC
authors.lastname: Whittle
authors.forename: A B
authors.initials: AB
authors.lastname: Rickinson
mesh_terms: D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D017124:Conserved Sequence; D003601:Cytotoxicity Tests, Immunologic; D004268:DNA-Binding Proteins / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens; D005714:Gambia; D015797:HLA-B35 Antigen / Q000235:genetics* / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
chemical_list: D000956:Antigens, Viral; D004268:DNA-Binding Proteins; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D015797:HLA-B35 Antigen