Sequences of cytotoxic T-lymphocyte epitopes in the Epstein-Barr virus (EBV) nuclear antigen-3B gene in a Japanese population with or without EBV-positive lymphoid malignancies

Latent infection antigens of EBV, including EBV nuclear antigens (EBNAs) an d latent membrane proteins, are expressed in latently infected and immortal ized B cells but work as target antigens for host cytotoxic T-lymphocyte (C TL) responses in an HLA class I-restricted manner. Among these latent antig ens, the immunodominant CTL epitopes in EBNA3B (EBNA3B 399-408 and EBNA3B 4 16-424) are well characterized, Mutations and strain differences in these s equences, compared to the prototype A sequence, reduce CTL responses to lat ently infected B cells, These EBNA3B CTL epitopes in the normal Japanese po pulation and in 2 lymphoid neoplasias, pyothorax-associated lymphoma (PAL) and nasal natural killer-cell lymphoma, were directly sequenced by PCR. Mos t EBV in peripheral blood leukocytes (PBLs) from healthy Japanese donors ex hibited the prototype A sequence, with mutations in approximately 20% (3/16 ), The sequence of EBNA3B CTL epitopes in lymphoma tissue was obtained in 6 PAL cases, and 5 exhibited mutations or strain differences compared to the prototype A sequence. Furthermore, the EBNA3B sequence in PAL tissue was d ifferent from that in PBLs of the same patient or I of the sequences found in PBLs, However, the EBNA3B gene in nasal lymphoma tissues exhibited predo minantly the prototype A sequence. Because PAL cells expressed EBNA3B mRNA, detected by RT-PCR, but nasal lymphoma cells did not, mutations and strain differences of the sequences of EBNA3B CTL epitopes were specific findings in EBNA3B-positive lymphomas. (C) 2000 Wiley-Liss, Inc.