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) and latent membrane proteins, are expressed in latently infected and immortalized B cells but work as target antigens for host cytotoxic T-lymphocyte (CTL) responses in an HLA class I-restricted manner. Among these latent antigens, the immunodominant CTL epitopes in EBNA3B (EBNA3B 399-408 and EBNA3B 416-424) are well characterized. Mutations and strain differences in these sequences, compared to the prototype A sequence, reduce CTL responses to latently infected B cells. These EBNA3B CTL epitopes in the normal Japanese population and in 2 lymphoid neoplasias, pyothorax-associated lymphoma (PAL) and nasal natural killer-cell lymphoma, were directly sequenced by PCR. Most EBV in peripheral blood leukocytes (PBLs) from healthy Japanese donors exhibited 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 different from that in PBLs of the same patient or 1 of the sequences found in PBLs. However, the EBNA3B gene in nasal lymphoma tissues exhibited predominantly 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.