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

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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 3 A 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.

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