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.
Kanno
H
H
Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Nakatsuka
S
S
Iuchi
K
K
Aozasa
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002051:Burkitt Lymphoma; D000939:Epitopes / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007564:Japan; D008223:Lymphoma / Q000276:immunology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D015395:Histocompatibility Antigens Class I; C411724:lymphocryptovirus nuclear antigen 3B