Selected amino acid change encoding Epstein-Barr virus-specific T cell epitope of the LMP2A gene in Japanese nasal NK/T cell lymphoma patients.

Nasal natural killer (NK)/T cell lymphoma is a peculiar lymphoma with a unique immunophenotype. Etiologically, in 1990, the authors first demonstrated the presence of Epstein-Barr virus (EBV) genomes and their products in this lymphoma. EBV-specific cytotoxic T lymphocytes (CTL) are very important in controlling the long-term persistence of EBV infection. Amino acid changes encoding the CTL epitope on the lymphoma cells may result in a reduced CTL response. We focused on two major CTL epitopes SSCSSCPLSK (codon 340 to 349) and FLYALALLLL (codon 356 to 364) of the LMP2A gene and determined the sequence isolated from nasal NK/T cell lymphoma tissues. All isolates from 7 nasal NK/T cell lymphomas showed the same amino acid change from serine to threonine at codon 348 in the CTL epitope SSCSSCPLSK. Threonine or serine substitution at codon 348 was almost equally observed in peripheral blood EBV isolates from healthy individuals in various ethnic origins. The predominant threonine substitution of nasal NK/T cell lymphoma patients may represent disease-associated polymorphism rather than a geographic or race-associated polymorphism. The LMP2A strain including threonine substitution at codon 348 may be selected within tumors and play a role for tumor genesis in Japanese patients with nasal NK/T cell lymphoma through reduced immune recognition.